id sid tid token lemma pos cord-021063-4y8m33ea 1 1 key key NN cord-021063-4y8m33ea 1 2 : : : cord-021063-4y8m33ea 2 1 cord-021063 cord-021063 NNP cord-021063-4y8m33ea 2 2 - - HYPH cord-021063-4y8m33ea 2 3 4y8m33ea 4y8m33ea CD cord-021063-4y8m33ea 2 4 authors author NNS cord-021063-4y8m33ea 2 5 : : : cord-021063-4y8m33ea 2 6 Hug hug VB cord-021063-4y8m33ea 2 7 , , , cord-021063-4y8m33ea 2 8 Peter Peter NNP cord-021063-4y8m33ea 2 9 ; ; : cord-021063-4y8m33ea 2 10 Sleight Sleight NNP cord-021063-4y8m33ea 2 11 , , , cord-021063-4y8m33ea 3 1 Richard Richard NNP cord-021063-4y8m33ea 3 2 G. G. NNP cord-021063-4y8m33ea 3 3 title title NN cord-021063-4y8m33ea 3 4 : : : cord-021063-4y8m33ea 3 5 Chapter chapter NN cord-021063-4y8m33ea 3 6 18 18 CD cord-021063-4y8m33ea 4 1 The the DT cord-021063-4y8m33ea 4 2 advantages advantage NNS cord-021063-4y8m33ea 4 3 of of IN cord-021063-4y8m33ea 4 4 liposome liposome NN cord-021063-4y8m33ea 4 5 - - HYPH cord-021063-4y8m33ea 4 6 based base VBN cord-021063-4y8m33ea 4 7 gene gene NN cord-021063-4y8m33ea 4 8 therapy therapy NN cord-021063-4y8m33ea 4 9 : : : cord-021063-4y8m33ea 4 10 A a DT cord-021063-4y8m33ea 4 11 comparison comparison NN cord-021063-4y8m33ea 4 12 of of IN cord-021063-4y8m33ea 4 13 viral viral JJ cord-021063-4y8m33ea 4 14 versus versus IN cord-021063-4y8m33ea 4 15 liposome liposome NN cord-021063-4y8m33ea 4 16 - - HYPH cord-021063-4y8m33ea 4 17 based base VBN cord-021063-4y8m33ea 4 18 gene gene NN cord-021063-4y8m33ea 4 19 delivery delivery NN cord-021063-4y8m33ea 4 20 date date NN cord-021063-4y8m33ea 4 21 : : : cord-021063-4y8m33ea 4 22 2007 2007 CD cord-021063-4y8m33ea 4 23 - - SYM cord-021063-4y8m33ea 4 24 09 09 CD cord-021063-4y8m33ea 4 25 - - HYPH cord-021063-4y8m33ea 4 26 02 02 CD cord-021063-4y8m33ea 4 27 journal journal NN cord-021063-4y8m33ea 4 28 : : : cord-021063-4y8m33ea 4 29 nan nan NNP cord-021063-4y8m33ea 4 30 DOI DOI NNP cord-021063-4y8m33ea 4 31 : : : cord-021063-4y8m33ea 4 32 10.1016 10.1016 CD cord-021063-4y8m33ea 4 33 / / SYM cord-021063-4y8m33ea 4 34 s1569 s1569 CD cord-021063-4y8m33ea 4 35 - - HYPH cord-021063-4y8m33ea 4 36 2582(97)80043 2582(97)80043 CD cord-021063-4y8m33ea 4 37 - - HYPH cord-021063-4y8m33ea 4 38 8 8 CD cord-021063-4y8m33ea 4 39 sha sha NN cord-021063-4y8m33ea 4 40 : : : cord-021063-4y8m33ea 4 41 a347a23ce4452adcb772163e22fa377854605ad8 a347a23ce4452adcb772163e22fa377854605ad8 XX cord-021063-4y8m33ea 4 42 doc_id doc_id CD cord-021063-4y8m33ea 4 43 : : : cord-021063-4y8m33ea 4 44 21063 21063 CD cord-021063-4y8m33ea 4 45 cord_uid cord_uid NNS cord-021063-4y8m33ea 4 46 : : : cord-021063-4y8m33ea 5 1 4y8m33ea 4y8m33ea LS cord-021063-4y8m33ea 6 1 Viruses virus NNS cord-021063-4y8m33ea 6 2 have have VBP cord-021063-4y8m33ea 6 3 evolved evolve VBN cord-021063-4y8m33ea 6 4 in in IN cord-021063-4y8m33ea 6 5 such such PDT cord-021063-4y8m33ea 6 6 a a DT cord-021063-4y8m33ea 6 7 way way NN cord-021063-4y8m33ea 6 8 they -PRON- PRP cord-021063-4y8m33ea 6 9 are be VBP cord-021063-4y8m33ea 6 10 able able JJ cord-021063-4y8m33ea 6 11 to to TO cord-021063-4y8m33ea 6 12 efficiently efficiently RB cord-021063-4y8m33ea 6 13 introduce introduce VB cord-021063-4y8m33ea 6 14 and and CC cord-021063-4y8m33ea 6 15 express express VB cord-021063-4y8m33ea 6 16 exogenous exogenous JJ cord-021063-4y8m33ea 6 17 genes gene NNS cord-021063-4y8m33ea 6 18 in in IN cord-021063-4y8m33ea 6 19 eukaryotic eukaryotic JJ cord-021063-4y8m33ea 6 20 cells cell NNS cord-021063-4y8m33ea 6 21 . . . cord-021063-4y8m33ea 7 1 Most Most JJS cord-021063-4y8m33ea 7 2 viruses virus NNS cord-021063-4y8m33ea 7 3 need need VBP cord-021063-4y8m33ea 7 4 to to TO cord-021063-4y8m33ea 7 5 maintain maintain VB cord-021063-4y8m33ea 7 6 high high JJ cord-021063-4y8m33ea 7 7 - - HYPH cord-021063-4y8m33ea 7 8 level level NN cord-021063-4y8m33ea 7 9 expression expression NN cord-021063-4y8m33ea 7 10 of of IN cord-021063-4y8m33ea 7 11 their -PRON- PRP$ cord-021063-4y8m33ea 7 12 proteins protein NNS cord-021063-4y8m33ea 7 13 for for IN cord-021063-4y8m33ea 7 14 only only RB cord-021063-4y8m33ea 7 15 a a DT cord-021063-4y8m33ea 7 16 short short JJ cord-021063-4y8m33ea 7 17 time time NN cord-021063-4y8m33ea 7 18 and and CC cord-021063-4y8m33ea 7 19 need nee MD cord-021063-4y8m33ea 7 20 not not RB cord-021063-4y8m33ea 7 21 be be VB cord-021063-4y8m33ea 7 22 concerned concern VBN cord-021063-4y8m33ea 7 23 with with IN cord-021063-4y8m33ea 7 24 the the DT cord-021063-4y8m33ea 7 25 viability viability NN cord-021063-4y8m33ea 7 26 of of IN cord-021063-4y8m33ea 7 27 the the DT cord-021063-4y8m33ea 7 28 host host NN cord-021063-4y8m33ea 7 29 cell cell NN cord-021063-4y8m33ea 7 30 after after IN cord-021063-4y8m33ea 7 31 infection infection NN cord-021063-4y8m33ea 7 32 . . . cord-021063-4y8m33ea 8 1 Attempts attempt NNS cord-021063-4y8m33ea 8 2 to to TO cord-021063-4y8m33ea 8 3 modify modify VB cord-021063-4y8m33ea 8 4 a a DT cord-021063-4y8m33ea 8 5 virus virus NN cord-021063-4y8m33ea 8 6 into into IN cord-021063-4y8m33ea 8 7 a a DT cord-021063-4y8m33ea 8 8 gene gene NN cord-021063-4y8m33ea 8 9 therapy therapy NN cord-021063-4y8m33ea 8 10 vector vector NN cord-021063-4y8m33ea 8 11 can can MD cord-021063-4y8m33ea 8 12 be be VB cord-021063-4y8m33ea 8 13 hampered hamper VBN cord-021063-4y8m33ea 8 14 by by IN cord-021063-4y8m33ea 8 15 this this DT cord-021063-4y8m33ea 8 16 conflict conflict NN cord-021063-4y8m33ea 8 17 . . . cord-021063-4y8m33ea 9 1 Virus virus NN cord-021063-4y8m33ea 9 2 - - HYPH cord-021063-4y8m33ea 9 3 based base VBN cord-021063-4y8m33ea 9 4 methods method NNS cord-021063-4y8m33ea 9 5 of of IN cord-021063-4y8m33ea 9 6 gene gene NN cord-021063-4y8m33ea 9 7 therapy therapy NN cord-021063-4y8m33ea 9 8 are be VBP cord-021063-4y8m33ea 9 9 likely likely JJ cord-021063-4y8m33ea 9 10 to to TO cord-021063-4y8m33ea 9 11 be be VB cord-021063-4y8m33ea 9 12 most most RBS cord-021063-4y8m33ea 9 13 useful useful JJ cord-021063-4y8m33ea 9 14 in in IN cord-021063-4y8m33ea 9 15 applications application NNS cord-021063-4y8m33ea 9 16 that that WDT cord-021063-4y8m33ea 9 17 require require VBP cord-021063-4y8m33ea 9 18 a a DT cord-021063-4y8m33ea 9 19 burst burst NN cord-021063-4y8m33ea 9 20 of of IN cord-021063-4y8m33ea 9 21 high high JJ cord-021063-4y8m33ea 9 22 - - HYPH cord-021063-4y8m33ea 9 23 level level NN cord-021063-4y8m33ea 9 24 expression expression NN cord-021063-4y8m33ea 9 25 in in IN cord-021063-4y8m33ea 9 26 many many JJ cord-021063-4y8m33ea 9 27 of of IN cord-021063-4y8m33ea 9 28 the the DT cord-021063-4y8m33ea 9 29 patient patient NN cord-021063-4y8m33ea 9 30 's 's POS cord-021063-4y8m33ea 9 31 cells cell NNS cord-021063-4y8m33ea 9 32 , , , cord-021063-4y8m33ea 9 33 such such JJ cord-021063-4y8m33ea 9 34 as as IN cord-021063-4y8m33ea 9 35 in in IN cord-021063-4y8m33ea 9 36 cancer cancer NN cord-021063-4y8m33ea 9 37 therapy therapy NN cord-021063-4y8m33ea 9 38 . . . cord-021063-4y8m33ea 10 1 Liposomal Liposomal NNP cord-021063-4y8m33ea 10 2 methods method NNS cord-021063-4y8m33ea 10 3 of of IN cord-021063-4y8m33ea 10 4 gene gene NN cord-021063-4y8m33ea 10 5 therapy therapy NN cord-021063-4y8m33ea 10 6 are be VBP cord-021063-4y8m33ea 10 7 flexible flexible JJ cord-021063-4y8m33ea 10 8 in in IN cord-021063-4y8m33ea 10 9 that that IN cord-021063-4y8m33ea 10 10 all all PDT cord-021063-4y8m33ea 10 11 the the DT cord-021063-4y8m33ea 10 12 components component NNS cord-021063-4y8m33ea 10 13 of of IN cord-021063-4y8m33ea 10 14 the the DT cord-021063-4y8m33ea 10 15 system system NN cord-021063-4y8m33ea 10 16 are be VBP cord-021063-4y8m33ea 10 17 controlled control VBN cord-021063-4y8m33ea 10 18 by by IN cord-021063-4y8m33ea 10 19 designers designer NNS cord-021063-4y8m33ea 10 20 . . . cord-021063-4y8m33ea 11 1 As as IN cord-021063-4y8m33ea 11 2 these these DT cord-021063-4y8m33ea 11 3 systems system NNS cord-021063-4y8m33ea 11 4 have have VBP cord-021063-4y8m33ea 11 5 become become VBN cord-021063-4y8m33ea 11 6 more more RBR cord-021063-4y8m33ea 11 7 sophisticated sophisticated JJ cord-021063-4y8m33ea 11 8 , , , cord-021063-4y8m33ea 11 9 they -PRON- PRP cord-021063-4y8m33ea 11 10 have have VBP cord-021063-4y8m33ea 11 11 begun begin VBN cord-021063-4y8m33ea 11 12 to to TO cord-021063-4y8m33ea 11 13 take take VB cord-021063-4y8m33ea 11 14 on on RP cord-021063-4y8m33ea 11 15 several several JJ cord-021063-4y8m33ea 11 16 characteristics characteristic NNS cord-021063-4y8m33ea 11 17 of of IN cord-021063-4y8m33ea 11 18 the the DT cord-021063-4y8m33ea 11 19 viruses virus NNS cord-021063-4y8m33ea 11 20 that that WDT cord-021063-4y8m33ea 11 21 they -PRON- PRP cord-021063-4y8m33ea 11 22 are be VBP cord-021063-4y8m33ea 11 23 intended intend VBN cord-021063-4y8m33ea 11 24 to to TO cord-021063-4y8m33ea 11 25 replace replace VB cord-021063-4y8m33ea 11 26 . . . cord-021063-4y8m33ea 12 1 The the DT cord-021063-4y8m33ea 12 2 use use NN cord-021063-4y8m33ea 12 3 of of IN cord-021063-4y8m33ea 12 4 basic basic JJ cord-021063-4y8m33ea 12 5 substances substance NNS cord-021063-4y8m33ea 12 6 to to TO cord-021063-4y8m33ea 12 7 condense condense VB cord-021063-4y8m33ea 12 8 DNA DNA NNP cord-021063-4y8m33ea 12 9 has have VBZ cord-021063-4y8m33ea 12 10 increased increase VBN cord-021063-4y8m33ea 12 11 the the DT cord-021063-4y8m33ea 12 12 efficiency efficiency NN cord-021063-4y8m33ea 12 13 of of IN cord-021063-4y8m33ea 12 14 encapsulation encapsulation NN cord-021063-4y8m33ea 12 15 . . . cord-021063-4y8m33ea 13 1 The the DT cord-021063-4y8m33ea 13 2 addition addition NN cord-021063-4y8m33ea 13 3 of of IN cord-021063-4y8m33ea 13 4 nucleophilic nucleophilic JJ cord-021063-4y8m33ea 13 5 proteins protein NNS cord-021063-4y8m33ea 13 6 raises raise VBZ cord-021063-4y8m33ea 13 7 the the DT cord-021063-4y8m33ea 13 8 efficiency efficiency NN cord-021063-4y8m33ea 13 9 of of IN cord-021063-4y8m33ea 13 10 transfection transfection NN cord-021063-4y8m33ea 13 11 . . . cord-021063-4y8m33ea 14 1 By by IN cord-021063-4y8m33ea 14 2 adding add VBG cord-021063-4y8m33ea 14 3 antibodies antibody NNS cord-021063-4y8m33ea 14 4 or or CC cord-021063-4y8m33ea 14 5 other other JJ cord-021063-4y8m33ea 14 6 targeting target VBG cord-021063-4y8m33ea 14 7 molecules molecule NNS cord-021063-4y8m33ea 14 8 to to IN cord-021063-4y8m33ea 14 9 the the DT cord-021063-4y8m33ea 14 10 surface surface NN cord-021063-4y8m33ea 14 11 of of IN cord-021063-4y8m33ea 14 12 liposomes liposome NNS cord-021063-4y8m33ea 14 13 , , , cord-021063-4y8m33ea 14 14 preferential preferential JJ cord-021063-4y8m33ea 14 15 binding binding NN cord-021063-4y8m33ea 14 16 of of IN cord-021063-4y8m33ea 14 17 vesicles vesicle NNS cord-021063-4y8m33ea 14 18 to to IN cord-021063-4y8m33ea 14 19 a a DT cord-021063-4y8m33ea 14 20 desired desire VBN cord-021063-4y8m33ea 14 21 cell cell NN cord-021063-4y8m33ea 14 22 type type NN cord-021063-4y8m33ea 14 23 has have VBZ cord-021063-4y8m33ea 14 24 been be VBN cord-021063-4y8m33ea 14 25 increased increase VBN cord-021063-4y8m33ea 14 26 . . . cord-021063-4y8m33ea 15 1 Gene gene NN cord-021063-4y8m33ea 15 2 therapy therapy NN cord-021063-4y8m33ea 15 3 as as IN cord-021063-4y8m33ea 15 4 a a DT cord-021063-4y8m33ea 15 5 treatment treatment NN cord-021063-4y8m33ea 15 6 for for IN cord-021063-4y8m33ea 15 7 human human JJ cord-021063-4y8m33ea 15 8 disease disease NN cord-021063-4y8m33ea 15 9 is be VBZ cord-021063-4y8m33ea 15 10 in in IN cord-021063-4y8m33ea 15 11 a a DT cord-021063-4y8m33ea 15 12 stage stage NN cord-021063-4y8m33ea 15 13 of of IN cord-021063-4y8m33ea 15 14 intensive intensive JJ cord-021063-4y8m33ea 15 15 development development NN cord-021063-4y8m33ea 15 16 . . . cord-021063-4y8m33ea 16 1 Already already RB cord-021063-4y8m33ea 16 2 in in IN cord-021063-4y8m33ea 16 3 limited limited JJ cord-021063-4y8m33ea 16 4 use use NN cord-021063-4y8m33ea 16 5 as as IN cord-021063-4y8m33ea 16 6 an an DT cord-021063-4y8m33ea 16 7 experimental experimental JJ cord-021063-4y8m33ea 16 8 therapy therapy NN cord-021063-4y8m33ea 16 9 for for IN cord-021063-4y8m33ea 16 10 cancer cancer NN cord-021063-4y8m33ea 17 1 ( ( -LRB- cord-021063-4y8m33ea 17 2 Oldfield Oldfield NNP cord-021063-4y8m33ea 17 3 et et NNP cord-021063-4y8m33ea 17 4 al al NNP cord-021063-4y8m33ea 17 5 . . NNP cord-021063-4y8m33ea 17 6 , , , cord-021063-4y8m33ea 17 7 1993 1993 CD cord-021063-4y8m33ea 17 8 ; ; : cord-021063-4y8m33ea 18 1 Nabel Nabel NNP cord-021063-4y8m33ea 18 2 et et NNP cord-021063-4y8m33ea 18 3 al al NNP cord-021063-4y8m33ea 18 4 . . NNP cord-021063-4y8m33ea 18 5 , , , cord-021063-4y8m33ea 18 6 1993 1993 CD cord-021063-4y8m33ea 18 7 ) ) -RRB- cord-021063-4y8m33ea 18 8 and and CC cord-021063-4y8m33ea 18 9 inborn inborn JJ cord-021063-4y8m33ea 18 10 errors error NNS cord-021063-4y8m33ea 18 11 of of IN cord-021063-4y8m33ea 18 12 metabolism metabolism NN cord-021063-4y8m33ea 19 1 ( ( -LRB- cord-021063-4y8m33ea 19 2 Hoogerbrugge Hoogerbrugge NNP cord-021063-4y8m33ea 19 3 et et NNP cord-021063-4y8m33ea 19 4 al al NNP cord-021063-4y8m33ea 19 5 . . . cord-021063-4y8m33ea 20 1 , , , cord-021063-4y8m33ea 20 2 1992 1992 CD cord-021063-4y8m33ea 20 3 ; ; : cord-021063-4y8m33ea 20 4 Morgan Morgan NNP cord-021063-4y8m33ea 20 5 and and CC cord-021063-4y8m33ea 20 6 Anderson Anderson NNP cord-021063-4y8m33ea 20 7 , , , cord-021063-4y8m33ea 20 8 1993 1993 CD cord-021063-4y8m33ea 20 9 ) ) -RRB- cord-021063-4y8m33ea 20 10 , , , cord-021063-4y8m33ea 20 11 it -PRON- PRP cord-021063-4y8m33ea 20 12 will will MD cord-021063-4y8m33ea 20 13 become become VB cord-021063-4y8m33ea 20 14 a a DT cord-021063-4y8m33ea 20 15 tool tool NN cord-021063-4y8m33ea 20 16 to to TO cord-021063-4y8m33ea 20 17 treat treat VB cord-021063-4y8m33ea 20 18 diseases disease NNS cord-021063-4y8m33ea 20 19 that that WDT cord-021063-4y8m33ea 20 20 are be VBP cord-021063-4y8m33ea 20 21 currently currently RB cord-021063-4y8m33ea 20 22 difficult difficult JJ cord-021063-4y8m33ea 20 23 to to TO cord-021063-4y8m33ea 20 24 manage manage VB cord-021063-4y8m33ea 20 25 . . . cord-021063-4y8m33ea 21 1 There there EX cord-021063-4y8m33ea 21 2 are be VBP cord-021063-4y8m33ea 21 3 many many JJ cord-021063-4y8m33ea 21 4 competing compete VBG cord-021063-4y8m33ea 21 5 strategies strategy NNS cord-021063-4y8m33ea 21 6 being be VBG cord-021063-4y8m33ea 21 7 developed develop VBN cord-021063-4y8m33ea 21 8 to to TO cord-021063-4y8m33ea 21 9 introduce introduce VB cord-021063-4y8m33ea 21 10 exogenous exogenous JJ cord-021063-4y8m33ea 21 11 genes gene NNS cord-021063-4y8m33ea 21 12 into into IN cord-021063-4y8m33ea 21 13 a a DT cord-021063-4y8m33ea 21 14 subset subset NN cord-021063-4y8m33ea 21 15 of of IN cord-021063-4y8m33ea 21 16 cells cell NNS cord-021063-4y8m33ea 21 17 of of IN cord-021063-4y8m33ea 21 18 a a DT cord-021063-4y8m33ea 21 19 patient patient NN cord-021063-4y8m33ea 21 20 . . . cord-021063-4y8m33ea 22 1 Several several JJ cord-021063-4y8m33ea 22 2 of of IN cord-021063-4y8m33ea 22 3 these these DT cord-021063-4y8m33ea 22 4 are be VBP cord-021063-4y8m33ea 22 5 likely likely JJ cord-021063-4y8m33ea 22 6 to to TO cord-021063-4y8m33ea 22 7 proceed proceed VB cord-021063-4y8m33ea 22 8 to to IN cord-021063-4y8m33ea 22 9 clinical clinical JJ cord-021063-4y8m33ea 22 10 application application NN cord-021063-4y8m33ea 22 11 . . . cord-021063-4y8m33ea 23 1 Deciding decide VBG cord-021063-4y8m33ea 23 2 which which WDT cord-021063-4y8m33ea 23 3 therapeutic therapeutic JJ cord-021063-4y8m33ea 23 4 strategy strategy NN cord-021063-4y8m33ea 23 5 is be VBZ cord-021063-4y8m33ea 23 6 best well RBS cord-021063-4y8m33ea 23 7 suited suit VBN cord-021063-4y8m33ea 23 8 for for IN cord-021063-4y8m33ea 23 9 a a DT cord-021063-4y8m33ea 23 10 given give VBN cord-021063-4y8m33ea 23 11 disease disease NN cord-021063-4y8m33ea 23 12 will will MD cord-021063-4y8m33ea 23 13 require require VB cord-021063-4y8m33ea 23 14 an an DT cord-021063-4y8m33ea 23 15 understanding understanding NN cord-021063-4y8m33ea 23 16 of of IN cord-021063-4y8m33ea 23 17 the the DT cord-021063-4y8m33ea 23 18 underlying underlying JJ cord-021063-4y8m33ea 23 19 biology biology NN cord-021063-4y8m33ea 23 20 of of IN cord-021063-4y8m33ea 23 21 the the DT cord-021063-4y8m33ea 23 22 disease disease NN cord-021063-4y8m33ea 23 23 , , , cord-021063-4y8m33ea 23 24 as as RB cord-021063-4y8m33ea 23 25 well well RB cord-021063-4y8m33ea 23 26 as as IN cord-021063-4y8m33ea 23 27 the the DT cord-021063-4y8m33ea 23 28 therapy therapy NN cord-021063-4y8m33ea 23 29 . . . cord-021063-4y8m33ea 24 1 In in IN cord-021063-4y8m33ea 24 2 using use VBG cord-021063-4y8m33ea 24 3 this this DT cord-021063-4y8m33ea 24 4 chapter chapter NN cord-021063-4y8m33ea 24 5 to to TO cord-021063-4y8m33ea 24 6 learn learn VB cord-021063-4y8m33ea 24 7 about about IN cord-021063-4y8m33ea 24 8 liposomal liposomal JJ cord-021063-4y8m33ea 24 9 methods method NNS cord-021063-4y8m33ea 24 10 of of IN cord-021063-4y8m33ea 24 11 gene gene NN cord-021063-4y8m33ea 24 12 therapy therapy NN cord-021063-4y8m33ea 24 13 , , , cord-021063-4y8m33ea 24 14 one one PRP cord-021063-4y8m33ea 24 15 should should MD cord-021063-4y8m33ea 24 16 remember remember VB cord-021063-4y8m33ea 24 17 that that IN cord-021063-4y8m33ea 24 18 the the DT cord-021063-4y8m33ea 24 19 material material NN cord-021063-4y8m33ea 24 20 presented present VBN cord-021063-4y8m33ea 24 21 here here RB cord-021063-4y8m33ea 24 22 is be VBZ cord-021063-4y8m33ea 24 23 only only RB cord-021063-4y8m33ea 24 24 current current JJ cord-021063-4y8m33ea 24 25 as as IN cord-021063-4y8m33ea 24 26 of of IN cord-021063-4y8m33ea 24 27 January January NNP cord-021063-4y8m33ea 24 28 , , , cord-021063-4y8m33ea 24 29 1994 1994 CD cord-021063-4y8m33ea 24 30 . . . cord-021063-4y8m33ea 25 1 For for IN cord-021063-4y8m33ea 25 2 more more JJR cord-021063-4y8m33ea 25 3 recent recent JJ cord-021063-4y8m33ea 25 4 developments development NNS cord-021063-4y8m33ea 25 5 and and CC cord-021063-4y8m33ea 25 6 greater great JJR cord-021063-4y8m33ea 25 7 detail detail NN cord-021063-4y8m33ea 25 8 , , , cord-021063-4y8m33ea 25 9 it -PRON- PRP cord-021063-4y8m33ea 25 10 will will MD cord-021063-4y8m33ea 25 11 be be VB cord-021063-4y8m33ea 25 12 necessary necessary JJ cord-021063-4y8m33ea 25 13 to to TO cord-021063-4y8m33ea 25 14 consult consult VB cord-021063-4y8m33ea 25 15 the the DT cord-021063-4y8m33ea 25 16 original original JJ cord-021063-4y8m33ea 25 17 literature literature NN cord-021063-4y8m33ea 25 18 . . . cord-021063-4y8m33ea 26 1 Regardless regardless RB cord-021063-4y8m33ea 26 2 of of IN cord-021063-4y8m33ea 26 3 the the DT cord-021063-4y8m33ea 26 4 specific specific JJ cord-021063-4y8m33ea 26 5 disease disease NN cord-021063-4y8m33ea 26 6 being be VBG cord-021063-4y8m33ea 26 7 addressed address VBN cord-021063-4y8m33ea 26 8 by by IN cord-021063-4y8m33ea 26 9 gene gene NN cord-021063-4y8m33ea 26 10 therapy therapy NN cord-021063-4y8m33ea 26 11 , , , cord-021063-4y8m33ea 26 12 several several JJ cord-021063-4y8m33ea 26 13 factors factor NNS cord-021063-4y8m33ea 26 14 must must MD cord-021063-4y8m33ea 26 15 be be VB cord-021063-4y8m33ea 26 16 considered consider VBN cord-021063-4y8m33ea 26 17 before before IN cord-021063-4y8m33ea 26 18 one one CD cord-021063-4y8m33ea 26 19 treats treat VBZ cord-021063-4y8m33ea 26 20 patients patient NNS cord-021063-4y8m33ea 26 21 . . . cord-021063-4y8m33ea 27 1 The the DT cord-021063-4y8m33ea 27 2 first first JJ cord-021063-4y8m33ea 27 3 is be VBZ cord-021063-4y8m33ea 27 4 that that IN cord-021063-4y8m33ea 27 5 the the DT cord-021063-4y8m33ea 27 6 method method NN cord-021063-4y8m33ea 27 7 and and CC cord-021063-4y8m33ea 27 8 the the DT cord-021063-4y8m33ea 27 9 treatment treatment NN cord-021063-4y8m33ea 27 10 itself -PRON- PRP cord-021063-4y8m33ea 27 11 must must MD cord-021063-4y8m33ea 27 12 be be VB cord-021063-4y8m33ea 27 13 commensurate commensurate JJ cord-021063-4y8m33ea 27 14 with with IN cord-021063-4y8m33ea 27 15 the the DT cord-021063-4y8m33ea 27 16 severity severity NN cord-021063-4y8m33ea 27 17 of of IN cord-021063-4y8m33ea 27 18 the the DT cord-021063-4y8m33ea 27 19 disease disease NN cord-021063-4y8m33ea 27 20 . . . cord-021063-4y8m33ea 28 1 Gene gene NN cord-021063-4y8m33ea 28 2 therapy therapy NN cord-021063-4y8m33ea 28 3 will will MD cord-021063-4y8m33ea 28 4 not not RB cord-021063-4y8m33ea 28 5 be be VB cord-021063-4y8m33ea 28 6 the the DT cord-021063-4y8m33ea 28 7 preferred preferred JJ cord-021063-4y8m33ea 28 8 treatment treatment NN cord-021063-4y8m33ea 28 9 for for IN cord-021063-4y8m33ea 28 10 diseases disease NNS cord-021063-4y8m33ea 28 11 such such JJ cord-021063-4y8m33ea 28 12 as as IN cord-021063-4y8m33ea 28 13 phenylketonuria phenylketonuria NN cord-021063-4y8m33ea 28 14 or or CC cord-021063-4y8m33ea 28 15 galactosemia galactosemia NN cord-021063-4y8m33ea 28 16 , , , cord-021063-4y8m33ea 28 17 both both DT cord-021063-4y8m33ea 28 18 of of IN cord-021063-4y8m33ea 28 19 which which WDT cord-021063-4y8m33ea 28 20 can can MD cord-021063-4y8m33ea 28 21 be be VB cord-021063-4y8m33ea 28 22 treated treat VBN cord-021063-4y8m33ea 28 23 adequately adequately RB cord-021063-4y8m33ea 28 24 by by IN cord-021063-4y8m33ea 28 25 diet diet NN cord-021063-4y8m33ea 28 26 modification modification NN cord-021063-4y8m33ea 28 27 . . . cord-021063-4y8m33ea 29 1 A a DT cord-021063-4y8m33ea 29 2 more more RBR cord-021063-4y8m33ea 29 3 widely widely RB cord-021063-4y8m33ea 29 4 recognized recognize VBN cord-021063-4y8m33ea 29 5 problem problem NN cord-021063-4y8m33ea 29 6 is be VBZ cord-021063-4y8m33ea 29 7 that that IN cord-021063-4y8m33ea 29 8 the the DT cord-021063-4y8m33ea 29 9 treatment treatment NN cord-021063-4y8m33ea 29 10 may may MD cord-021063-4y8m33ea 29 11 , , , cord-021063-4y8m33ea 29 12 while while IN cord-021063-4y8m33ea 29 13 curing cure VBG cord-021063-4y8m33ea 29 14 the the DT cord-021063-4y8m33ea 29 15 disease disease NN cord-021063-4y8m33ea 29 16 , , , cord-021063-4y8m33ea 29 17 create create VB cord-021063-4y8m33ea 29 18 a a DT cord-021063-4y8m33ea 29 19 new new JJ cord-021063-4y8m33ea 29 20 one one CD cord-021063-4y8m33ea 29 21 in in IN cord-021063-4y8m33ea 29 22 the the DT cord-021063-4y8m33ea 29 23 process process NN cord-021063-4y8m33ea 29 24 . . . cord-021063-4y8m33ea 30 1 The the DT cord-021063-4y8m33ea 30 2 archetypal archetypal JJ cord-021063-4y8m33ea 30 3 concern concern NN cord-021063-4y8m33ea 30 4 is be VBZ cord-021063-4y8m33ea 30 5 the the DT cord-021063-4y8m33ea 30 6 generation generation NN cord-021063-4y8m33ea 30 7 of of IN cord-021063-4y8m33ea 30 8 insertional insertional JJ cord-021063-4y8m33ea 30 9 mutations mutation NNS cord-021063-4y8m33ea 30 10 by by IN cord-021063-4y8m33ea 30 11 the the DT cord-021063-4y8m33ea 30 12 integration integration NN cord-021063-4y8m33ea 30 13 of of IN cord-021063-4y8m33ea 30 14 the the DT cord-021063-4y8m33ea 30 15 curative curative JJ cord-021063-4y8m33ea 30 16 gene gene NN cord-021063-4y8m33ea 30 17 into into IN cord-021063-4y8m33ea 30 18 a a DT cord-021063-4y8m33ea 30 19 cellular cellular JJ cord-021063-4y8m33ea 30 20 protooncogene protooncogene NN cord-021063-4y8m33ea 30 21 , , , cord-021063-4y8m33ea 30 22 leading lead VBG cord-021063-4y8m33ea 30 23 to to IN cord-021063-4y8m33ea 30 24 cancer cancer NN cord-021063-4y8m33ea 30 25 in in IN cord-021063-4y8m33ea 30 26 the the DT cord-021063-4y8m33ea 30 27 " " `` cord-021063-4y8m33ea 30 28 cured cure VBN cord-021063-4y8m33ea 30 29 " " '' cord-021063-4y8m33ea 30 30 patient patient JJ cord-021063-4y8m33ea 30 31 . . . cord-021063-4y8m33ea 31 1 Once once RB cord-021063-4y8m33ea 31 2 a a DT cord-021063-4y8m33ea 31 3 method method NN cord-021063-4y8m33ea 31 4 has have VBZ cord-021063-4y8m33ea 31 5 been be VBN cord-021063-4y8m33ea 31 6 determined determine VBN cord-021063-4y8m33ea 31 7 to to TO cord-021063-4y8m33ea 31 8 be be VB cord-021063-4y8m33ea 31 9 reasonably reasonably RB cord-021063-4y8m33ea 31 10 safe safe JJ cord-021063-4y8m33ea 31 11 for for IN cord-021063-4y8m33ea 31 12 the the DT cord-021063-4y8m33ea 31 13 patient patient NN cord-021063-4y8m33ea 31 14 , , , cord-021063-4y8m33ea 31 15 it -PRON- PRP cord-021063-4y8m33ea 31 16 must must MD cord-021063-4y8m33ea 31 17 be be VB cord-021063-4y8m33ea 31 18 shown show VBN cord-021063-4y8m33ea 31 19 not not RB cord-021063-4y8m33ea 31 20 to to TO cord-021063-4y8m33ea 31 21 present present VB cord-021063-4y8m33ea 31 22 a a DT cord-021063-4y8m33ea 31 23 danger danger NN cord-021063-4y8m33ea 31 24 to to IN cord-021063-4y8m33ea 31 25 others other NNS cord-021063-4y8m33ea 31 26 . . . cord-021063-4y8m33ea 32 1 This this DT cord-021063-4y8m33ea 32 2 problem problem NN cord-021063-4y8m33ea 32 3 has have VBZ cord-021063-4y8m33ea 32 4 hampered hamper VBN cord-021063-4y8m33ea 32 5 the the DT cord-021063-4y8m33ea 32 6 widespread widespread JJ cord-021063-4y8m33ea 32 7 use use NN cord-021063-4y8m33ea 32 8 of of IN cord-021063-4y8m33ea 32 9 viral viral JJ cord-021063-4y8m33ea 32 10 transfection transfection NN cord-021063-4y8m33ea 32 11 vectors vector NNS cord-021063-4y8m33ea 32 12 . . . cord-021063-4y8m33ea 33 1 Substantial substantial JJ cord-021063-4y8m33ea 33 2 progress progress NN cord-021063-4y8m33ea 33 3 has have VBZ cord-021063-4y8m33ea 33 4 been be VBN cord-021063-4y8m33ea 33 5 made make VBN cord-021063-4y8m33ea 33 6 in in IN cord-021063-4y8m33ea 33 7 the the DT cord-021063-4y8m33ea 33 8 construction construction NN cord-021063-4y8m33ea 33 9 of of IN cord-021063-4y8m33ea 33 10 replication replication NN cord-021063-4y8m33ea 33 11 - - HYPH cord-021063-4y8m33ea 33 12 defective defective JJ cord-021063-4y8m33ea 33 13 retroviral retroviral NN cord-021063-4y8m33ea 33 14 and and CC cord-021063-4y8m33ea 33 15 adenoviral adenoviral JJ cord-021063-4y8m33ea 33 16 vectors vector NNS cord-021063-4y8m33ea 33 17 . . . cord-021063-4y8m33ea 34 1 However however RB cord-021063-4y8m33ea 34 2 , , , cord-021063-4y8m33ea 34 3 the the DT cord-021063-4y8m33ea 34 4 possibility possibility NN cord-021063-4y8m33ea 34 5 remains remain VBZ cord-021063-4y8m33ea 34 6 that that IN cord-021063-4y8m33ea 34 7 superinfection superinfection NN cord-021063-4y8m33ea 34 8 with with IN cord-021063-4y8m33ea 34 9 wild wild JJ cord-021063-4y8m33ea 34 10 - - HYPH cord-021063-4y8m33ea 34 11 type type NN cord-021063-4y8m33ea 34 12 adenovirus adenovirus NN cord-021063-4y8m33ea 34 13 , , , cord-021063-4y8m33ea 34 14 or or CC cord-021063-4y8m33ea 34 15 insertion insertion NN cord-021063-4y8m33ea 34 16 of of IN cord-021063-4y8m33ea 34 17 a a DT cord-021063-4y8m33ea 34 18 wild wild JJ cord-021063-4y8m33ea 34 19 - - HYPH cord-021063-4y8m33ea 34 20 type type NN cord-021063-4y8m33ea 34 21 retrovirus retrovirus NN cord-021063-4y8m33ea 34 22 into into IN cord-021063-4y8m33ea 34 23 an an DT cord-021063-4y8m33ea 34 24 integrated integrate VBN cord-021063-4y8m33ea 34 25 defective defective JJ cord-021063-4y8m33ea 34 26 retroviral retroviral NN cord-021063-4y8m33ea 34 27 genome genome NN cord-021063-4y8m33ea 34 28 , , , cord-021063-4y8m33ea 34 29 can can MD cord-021063-4y8m33ea 34 30 generate generate VB cord-021063-4y8m33ea 34 31 new new JJ cord-021063-4y8m33ea 34 32 , , , cord-021063-4y8m33ea 34 33 infectious infectious JJ cord-021063-4y8m33ea 34 34 viral viral JJ cord-021063-4y8m33ea 34 35 particles particle NNS cord-021063-4y8m33ea 34 36 that that WDT cord-021063-4y8m33ea 34 37 could could MD cord-021063-4y8m33ea 34 38 contain contain VB cord-021063-4y8m33ea 34 39 an an DT cord-021063-4y8m33ea 34 40 oncogenic oncogenic JJ cord-021063-4y8m33ea 34 41 fragment fragment NN cord-021063-4y8m33ea 34 42 of of IN cord-021063-4y8m33ea 34 43 the the DT cord-021063-4y8m33ea 34 44 therapeutic therapeutic JJ cord-021063-4y8m33ea 34 45 gene gene NN cord-021063-4y8m33ea 34 46 . . . cord-021063-4y8m33ea 35 1 These these DT cord-021063-4y8m33ea 35 2 viral viral JJ cord-021063-4y8m33ea 35 3 particles particle NNS cord-021063-4y8m33ea 35 4 may may MD cord-021063-4y8m33ea 35 5 have have VB cord-021063-4y8m33ea 35 6 the the DT cord-021063-4y8m33ea 35 7 ability ability NN cord-021063-4y8m33ea 35 8 to to TO cord-021063-4y8m33ea 35 9 transfer transfer VB cord-021063-4y8m33ea 35 10 genes gene NNS cord-021063-4y8m33ea 35 11 between between IN cord-021063-4y8m33ea 35 12 a a DT cord-021063-4y8m33ea 35 13 patient patient NN cord-021063-4y8m33ea 35 14 's 's POS cord-021063-4y8m33ea 35 15 cells cell NNS cord-021063-4y8m33ea 35 16 , , , cord-021063-4y8m33ea 35 17 and and CC cord-021063-4y8m33ea 35 18 between between IN cord-021063-4y8m33ea 35 19 individuals individual NNS cord-021063-4y8m33ea 35 20 . . . cord-021063-4y8m33ea 36 1 In in IN cord-021063-4y8m33ea 36 2 order order NN cord-021063-4y8m33ea 36 3 for for IN cord-021063-4y8m33ea 36 4 a a DT cord-021063-4y8m33ea 36 5 method method NN cord-021063-4y8m33ea 36 6 of of IN cord-021063-4y8m33ea 36 7 gene gene NN cord-021063-4y8m33ea 36 8 therapy therapy NN cord-021063-4y8m33ea 36 9 to to TO cord-021063-4y8m33ea 36 10 be be VB cord-021063-4y8m33ea 36 11 useful useful JJ cord-021063-4y8m33ea 36 12 , , , cord-021063-4y8m33ea 36 13 it -PRON- PRP cord-021063-4y8m33ea 36 14 must must MD cord-021063-4y8m33ea 36 15 significantly significantly RB cord-021063-4y8m33ea 36 16 ameliorate ameliorate VB cord-021063-4y8m33ea 36 17 the the DT cord-021063-4y8m33ea 36 18 symptoms symptom NNS cord-021063-4y8m33ea 36 19 of of IN cord-021063-4y8m33ea 36 20 the the DT cord-021063-4y8m33ea 36 21 disease disease NN cord-021063-4y8m33ea 36 22 , , , cord-021063-4y8m33ea 36 23 and and CC cord-021063-4y8m33ea 36 24 halt halt VB cord-021063-4y8m33ea 36 25 the the DT cord-021063-4y8m33ea 36 26 progression progression NN cord-021063-4y8m33ea 36 27 of of IN cord-021063-4y8m33ea 36 28 the the DT cord-021063-4y8m33ea 36 29 disease disease NN cord-021063-4y8m33ea 36 30 state state NN cord-021063-4y8m33ea 36 31 for for IN cord-021063-4y8m33ea 36 32 a a DT cord-021063-4y8m33ea 36 33 significant significant JJ cord-021063-4y8m33ea 36 34 period period NN cord-021063-4y8m33ea 36 35 of of IN cord-021063-4y8m33ea 36 36 time time NN cord-021063-4y8m33ea 36 37 . . . cord-021063-4y8m33ea 37 1 Ideally ideally RB cord-021063-4y8m33ea 37 2 , , , cord-021063-4y8m33ea 37 3 the the DT cord-021063-4y8m33ea 37 4 disease disease NN cord-021063-4y8m33ea 37 5 would would MD cord-021063-4y8m33ea 37 6 be be VB cord-021063-4y8m33ea 37 7 cured cure VBN cord-021063-4y8m33ea 37 8 permanently permanently RB cord-021063-4y8m33ea 37 9 by by IN cord-021063-4y8m33ea 37 10 one one CD cord-021063-4y8m33ea 37 11 treatment treatment NN cord-021063-4y8m33ea 37 12 . . . cord-021063-4y8m33ea 38 1 Although although IN cord-021063-4y8m33ea 38 2 periodic periodic JJ cord-021063-4y8m33ea 38 3 retreatments retreatment NNS cord-021063-4y8m33ea 38 4 might may MD cord-021063-4y8m33ea 38 5 be be VB cord-021063-4y8m33ea 38 6 acceptable acceptable JJ cord-021063-4y8m33ea 38 7 , , , cord-021063-4y8m33ea 38 8 every every DT cord-021063-4y8m33ea 38 9 treatment treatment NN cord-021063-4y8m33ea 38 10 brings bring VBZ cord-021063-4y8m33ea 38 11 with with IN cord-021063-4y8m33ea 38 12 it -PRON- PRP cord-021063-4y8m33ea 38 13 the the DT cord-021063-4y8m33ea 38 14 possibility possibility NN cord-021063-4y8m33ea 38 15 of of IN cord-021063-4y8m33ea 38 16 insertional insertional JJ cord-021063-4y8m33ea 38 17 mutagenesis mutagenesis NN cord-021063-4y8m33ea 38 18 or or CC cord-021063-4y8m33ea 38 19 the the DT cord-021063-4y8m33ea 38 20 generation generation NN cord-021063-4y8m33ea 38 21 of of IN cord-021063-4y8m33ea 38 22 an an DT cord-021063-4y8m33ea 38 23 immune immune JJ cord-021063-4y8m33ea 38 24 response response NN cord-021063-4y8m33ea 38 25 to to IN cord-021063-4y8m33ea 38 26 the the DT cord-021063-4y8m33ea 38 27 therapeutic therapeutic JJ cord-021063-4y8m33ea 38 28 vector vector NN cord-021063-4y8m33ea 38 29 . . . cord-021063-4y8m33ea 39 1 The the DT cord-021063-4y8m33ea 39 2 final final JJ cord-021063-4y8m33ea 39 3 considerations consideration NNS cord-021063-4y8m33ea 39 4 involve involve VBP cord-021063-4y8m33ea 39 5 ease ease NN cord-021063-4y8m33ea 39 6 of of IN cord-021063-4y8m33ea 39 7 preparation preparation NN cord-021063-4y8m33ea 39 8 and and CC cord-021063-4y8m33ea 39 9 use use NN cord-021063-4y8m33ea 39 10 . . . cord-021063-4y8m33ea 40 1 Many many JJ cord-021063-4y8m33ea 40 2 candidate candidate NN cord-021063-4y8m33ea 40 3 vectors vector NNS cord-021063-4y8m33ea 40 4 , , , cord-021063-4y8m33ea 40 5 although although IN cord-021063-4y8m33ea 40 6 potentially potentially RB cord-021063-4y8m33ea 40 7 capable capable JJ cord-021063-4y8m33ea 40 8 of of IN cord-021063-4y8m33ea 40 9 introducing introduce VBG cord-021063-4y8m33ea 40 10 foreign foreign JJ cord-021063-4y8m33ea 40 11 genes gene NNS cord-021063-4y8m33ea 40 12 into into IN cord-021063-4y8m33ea 40 13 an an DT cord-021063-4y8m33ea 40 14 organism organism NN cord-021063-4y8m33ea 40 15 , , , cord-021063-4y8m33ea 40 16 are be VBP cord-021063-4y8m33ea 40 17 so so RB cord-021063-4y8m33ea 40 18 difficult difficult JJ cord-021063-4y8m33ea 40 19 to to TO cord-021063-4y8m33ea 40 20 generate generate VB cord-021063-4y8m33ea 40 21 , , , cord-021063-4y8m33ea 40 22 or or CC cord-021063-4y8m33ea 40 23 administer administer VB cord-021063-4y8m33ea 40 24 , , , cord-021063-4y8m33ea 40 25 that that IN cord-021063-4y8m33ea 40 26 it -PRON- PRP cord-021063-4y8m33ea 40 27 is be VBZ cord-021063-4y8m33ea 40 28 difficult difficult JJ cord-021063-4y8m33ea 40 29 to to TO cord-021063-4y8m33ea 40 30 envision envision VB cord-021063-4y8m33ea 40 31 their -PRON- PRP$ cord-021063-4y8m33ea 40 32 widespread widespread JJ cord-021063-4y8m33ea 40 33 adoption adoption NN cord-021063-4y8m33ea 40 34 . . . cord-021063-4y8m33ea 41 1 This this DT cord-021063-4y8m33ea 41 2 aspect aspect NN cord-021063-4y8m33ea 41 3 of of IN cord-021063-4y8m33ea 41 4 vector vector NN cord-021063-4y8m33ea 41 5 design design NN cord-021063-4y8m33ea 41 6 is be VBZ cord-021063-4y8m33ea 41 7 often often RB cord-021063-4y8m33ea 41 8 not not RB cord-021063-4y8m33ea 41 9 considered consider VBN cord-021063-4y8m33ea 41 10 until until IN cord-021063-4y8m33ea 41 11 after after IN cord-021063-4y8m33ea 41 12 the the DT cord-021063-4y8m33ea 41 13 vector vector NN cord-021063-4y8m33ea 41 14 is be VBZ cord-021063-4y8m33ea 41 15 developed develop VBN cord-021063-4y8m33ea 41 16 . . . cord-021063-4y8m33ea 42 1 Bearing bear VBG cord-021063-4y8m33ea 42 2 in in IN cord-021063-4y8m33ea 42 3 mind mind NN cord-021063-4y8m33ea 42 4 the the DT cord-021063-4y8m33ea 42 5 above above JJ cord-021063-4y8m33ea 42 6 considerations consideration NNS cord-021063-4y8m33ea 42 7 , , , cord-021063-4y8m33ea 42 8 let let VB cord-021063-4y8m33ea 42 9 us -PRON- PRP cord-021063-4y8m33ea 42 10 now now RB cord-021063-4y8m33ea 42 11 consider consider VB cord-021063-4y8m33ea 42 12 the the DT cord-021063-4y8m33ea 42 13 various various JJ cord-021063-4y8m33ea 42 14 approaches approach NNS cord-021063-4y8m33ea 42 15 being be VBG cord-021063-4y8m33ea 42 16 developed develop VBN cord-021063-4y8m33ea 42 17 to to TO cord-021063-4y8m33ea 42 18 create create VB cord-021063-4y8m33ea 42 19 vectors vector NNS cord-021063-4y8m33ea 42 20 for for IN cord-021063-4y8m33ea 42 21 gene gene NN cord-021063-4y8m33ea 42 22 therapy therapy NN cord-021063-4y8m33ea 42 23 . . . cord-021063-4y8m33ea 43 1 In in IN cord-021063-4y8m33ea 43 2 general general JJ cord-021063-4y8m33ea 43 3 , , , cord-021063-4y8m33ea 43 4 these these DT cord-021063-4y8m33ea 43 5 can can MD cord-021063-4y8m33ea 43 6 be be VB cord-021063-4y8m33ea 43 7 divided divide VBN cord-021063-4y8m33ea 43 8 into into IN cord-021063-4y8m33ea 43 9 three three CD cord-021063-4y8m33ea 43 10 groups group NNS cord-021063-4y8m33ea 43 11 : : : cord-021063-4y8m33ea 43 12 ( ( -LRB- cord-021063-4y8m33ea 43 13 i i NN cord-021063-4y8m33ea 43 14 ) ) -RRB- cord-021063-4y8m33ea 43 15 active active JJ cord-021063-4y8m33ea 43 16 viruses virus NNS cord-021063-4y8m33ea 43 17 , , , cord-021063-4y8m33ea 43 18 ( ( -LRB- cord-021063-4y8m33ea 43 19 ii ii NN cord-021063-4y8m33ea 43 20 ) ) -RRB- cord-021063-4y8m33ea 43 21 viral viral JJ cord-021063-4y8m33ea 43 22 mimics mimic VBZ cord-021063-4y8m33ea 43 23 that that WDT cord-021063-4y8m33ea 43 24 attempt attempt VBP cord-021063-4y8m33ea 43 25 to to TO cord-021063-4y8m33ea 43 26 reproduce reproduce VB cord-021063-4y8m33ea 43 27 a a DT cord-021063-4y8m33ea 43 28 subset subset NN cord-021063-4y8m33ea 43 29 of of IN cord-021063-4y8m33ea 43 30 viral viral JJ cord-021063-4y8m33ea 43 31 activities activity NNS cord-021063-4y8m33ea 43 32 in in IN cord-021063-4y8m33ea 43 33 a a DT cord-021063-4y8m33ea 43 34 synthetic synthetic JJ cord-021063-4y8m33ea 43 35 construct construct NN cord-021063-4y8m33ea 43 36 , , , cord-021063-4y8m33ea 43 37 and and CC cord-021063-4y8m33ea 43 38 ( ( -LRB- cord-021063-4y8m33ea 43 39 iii iii NN cord-021063-4y8m33ea 43 40 ) ) -RRB- cord-021063-4y8m33ea 43 41 artificial artificial JJ cord-021063-4y8m33ea 43 42 delivery delivery NN cord-021063-4y8m33ea 43 43 systems system NNS cord-021063-4y8m33ea 43 44 . . . cord-021063-4y8m33ea 44 1 Given give VBN cord-021063-4y8m33ea 44 2 the the DT cord-021063-4y8m33ea 44 3 amount amount NN cord-021063-4y8m33ea 44 4 of of IN cord-021063-4y8m33ea 44 5 effort effort NN cord-021063-4y8m33ea 44 6 being be VBG cord-021063-4y8m33ea 44 7 expended expend VBN cord-021063-4y8m33ea 44 8 on on IN cord-021063-4y8m33ea 44 9 the the DT cord-021063-4y8m33ea 44 10 development development NN cord-021063-4y8m33ea 44 11 of of IN cord-021063-4y8m33ea 44 12 these these DT cord-021063-4y8m33ea 44 13 systems system NNS cord-021063-4y8m33ea 44 14 , , , cord-021063-4y8m33ea 44 15 and and CC cord-021063-4y8m33ea 44 16 the the DT cord-021063-4y8m33ea 44 17 highly highly RB cord-021063-4y8m33ea 44 18 varied varied JJ cord-021063-4y8m33ea 44 19 nature nature NN cord-021063-4y8m33ea 44 20 of of IN cord-021063-4y8m33ea 44 21 the the DT cord-021063-4y8m33ea 44 22 intended intend VBN cord-021063-4y8m33ea 44 23 target target NN cord-021063-4y8m33ea 44 24 diseases disease NNS cord-021063-4y8m33ea 44 25 and and CC cord-021063-4y8m33ea 44 26 organs organ NNS cord-021063-4y8m33ea 44 27 , , , cord-021063-4y8m33ea 44 28 it -PRON- PRP cord-021063-4y8m33ea 44 29 is be VBZ cord-021063-4y8m33ea 44 30 likely likely JJ cord-021063-4y8m33ea 44 31 that that IN cord-021063-4y8m33ea 44 32 there there EX cord-021063-4y8m33ea 44 33 will will MD cord-021063-4y8m33ea 44 34 never never RB cord-021063-4y8m33ea 44 35 be be VB cord-021063-4y8m33ea 44 36 a a DT cord-021063-4y8m33ea 44 37 single single JJ cord-021063-4y8m33ea 44 38 best good JJS cord-021063-4y8m33ea 44 39 choice choice NN cord-021063-4y8m33ea 44 40 of of IN cord-021063-4y8m33ea 44 41 method method NN cord-021063-4y8m33ea 44 42 . . . cord-021063-4y8m33ea 45 1 Every every DT cord-021063-4y8m33ea 45 2 disease disease NN cord-021063-4y8m33ea 45 3 will will MD cord-021063-4y8m33ea 45 4 call call VB cord-021063-4y8m33ea 45 5 for for IN cord-021063-4y8m33ea 45 6 a a DT cord-021063-4y8m33ea 45 7 tailored tailor VBN cord-021063-4y8m33ea 45 8 strategy strategy NN cord-021063-4y8m33ea 45 9 that that WDT cord-021063-4y8m33ea 45 10 can can MD cord-021063-4y8m33ea 45 11 be be VB cord-021063-4y8m33ea 45 12 optimized optimize VBN cord-021063-4y8m33ea 45 13 to to IN cord-021063-4y8m33ea 45 14 best good JJS cord-021063-4y8m33ea 45 15 fit fit VB cord-021063-4y8m33ea 45 16 the the DT cord-021063-4y8m33ea 45 17 needs need NNS cord-021063-4y8m33ea 45 18 of of IN cord-021063-4y8m33ea 45 19 the the DT cord-021063-4y8m33ea 45 20 situation situation NN cord-021063-4y8m33ea 45 21 . . . cord-021063-4y8m33ea 46 1 Table table NN cord-021063-4y8m33ea 46 2 1 1 CD cord-021063-4y8m33ea 46 3 contains contain VBZ cord-021063-4y8m33ea 46 4 a a DT cord-021063-4y8m33ea 46 5 summary summary NN cord-021063-4y8m33ea 46 6 and and CC cord-021063-4y8m33ea 46 7 comparison comparison NN cord-021063-4y8m33ea 46 8 of of IN cord-021063-4y8m33ea 46 9 various various JJ cord-021063-4y8m33ea 46 10 gene gene NN cord-021063-4y8m33ea 46 11 therapy therapy NN cord-021063-4y8m33ea 46 12 delivery delivery NN cord-021063-4y8m33ea 46 13 vectors vector NNS cord-021063-4y8m33ea 46 14 . . . cord-021063-4y8m33ea 47 1 Ten ten CD cord-021063-4y8m33ea 47 2 years year NNS cord-021063-4y8m33ea 47 3 ago ago RB cord-021063-4y8m33ea 47 4 , , , cord-021063-4y8m33ea 47 5 it -PRON- PRP cord-021063-4y8m33ea 47 6 seemed seem VBD cord-021063-4y8m33ea 47 7 a a DT cord-021063-4y8m33ea 47 8 foregone foregone JJ cord-021063-4y8m33ea 47 9 conclusion conclusion NN cord-021063-4y8m33ea 47 10 that that IN cord-021063-4y8m33ea 47 11 retroviruses retrovirus NNS cord-021063-4y8m33ea 47 12 were be VBD cord-021063-4y8m33ea 47 13 the the DT cord-021063-4y8m33ea 47 14 only only JJ cord-021063-4y8m33ea 47 15 serious serious JJ cord-021063-4y8m33ea 47 16 candidate candidate NN cord-021063-4y8m33ea 47 17 for for IN cord-021063-4y8m33ea 47 18 an an DT cord-021063-4y8m33ea 47 19 eventual eventual JJ cord-021063-4y8m33ea 47 20 therapeutic therapeutic JJ cord-021063-4y8m33ea 47 21 vector vector NN cord-021063-4y8m33ea 47 22 . . . cord-021063-4y8m33ea 48 1 Today today NN cord-021063-4y8m33ea 48 2 , , , cord-021063-4y8m33ea 48 3 many many JJ cord-021063-4y8m33ea 48 4 different different JJ cord-021063-4y8m33ea 48 5 viral viral JJ cord-021063-4y8m33ea 48 6 vectors vector NNS cord-021063-4y8m33ea 48 7 are be VBP cord-021063-4y8m33ea 48 8 being be VBG cord-021063-4y8m33ea 48 9 considered consider VBN cord-021063-4y8m33ea 48 10 for for IN cord-021063-4y8m33ea 48 11 use use NN cord-021063-4y8m33ea 48 12 in in IN cord-021063-4y8m33ea 48 13 gene gene NN cord-021063-4y8m33ea 48 14 therapy therapy NN cord-021063-4y8m33ea 48 15 . . . cord-021063-4y8m33ea 49 1 Because because IN cord-021063-4y8m33ea 49 2 different different JJ cord-021063-4y8m33ea 49 3 viruses virus NNS cord-021063-4y8m33ea 49 4 target target VBP cord-021063-4y8m33ea 49 5 different different JJ cord-021063-4y8m33ea 49 6 cell cell NN cord-021063-4y8m33ea 49 7 types type NNS cord-021063-4y8m33ea 49 8 and and CC cord-021063-4y8m33ea 49 9 have have VBP cord-021063-4y8m33ea 49 10 different different JJ cord-021063-4y8m33ea 49 11 modes mode NNS cord-021063-4y8m33ea 49 12 of of IN cord-021063-4y8m33ea 49 13 replication replication NN cord-021063-4y8m33ea 49 14 , , , cord-021063-4y8m33ea 49 15 each each DT cord-021063-4y8m33ea 49 16 viral viral JJ cord-021063-4y8m33ea 49 17 delivery delivery NN cord-021063-4y8m33ea 49 18 system system NN cord-021063-4y8m33ea 49 19 may may MD cord-021063-4y8m33ea 49 20 be be VB cord-021063-4y8m33ea 49 21 best well RBS cord-021063-4y8m33ea 49 22 suited suit VBN cord-021063-4y8m33ea 49 23 for for IN cord-021063-4y8m33ea 49 24 treatment treatment NN cord-021063-4y8m33ea 49 25 of of IN cord-021063-4y8m33ea 49 26 different different JJ cord-021063-4y8m33ea 49 27 diseases disease NNS cord-021063-4y8m33ea 49 28 . . . cord-021063-4y8m33ea 50 1 The the DT cord-021063-4y8m33ea 50 2 viral viral JJ cord-021063-4y8m33ea 50 3 vectors vector NNS cord-021063-4y8m33ea 50 4 under under IN cord-021063-4y8m33ea 50 5 most most JJS cord-021063-4y8m33ea 50 6 active active JJ cord-021063-4y8m33ea 50 7 development development NN cord-021063-4y8m33ea 50 8 are be VBP cord-021063-4y8m33ea 50 9 retroviruses retrovirus NNS cord-021063-4y8m33ea 50 10 , , , cord-021063-4y8m33ea 50 11 adenoviruses adenovirus NNS cord-021063-4y8m33ea 50 12 , , , cord-021063-4y8m33ea 50 13 adeno adeno NN cord-021063-4y8m33ea 50 14 - - HYPH cord-021063-4y8m33ea 50 15 associated associate VBN cord-021063-4y8m33ea 50 16 virus virus NN cord-021063-4y8m33ea 50 17 , , , cord-021063-4y8m33ea 50 18 and and CC cord-021063-4y8m33ea 50 19 herpesviruses herpesviruses NNP cord-021063-4y8m33ea 50 20 . . . cord-021063-4y8m33ea 51 1 Some some DT cord-021063-4y8m33ea 51 2 general general JJ cord-021063-4y8m33ea 51 3 characteristics characteristic NNS cord-021063-4y8m33ea 51 4 of of IN cord-021063-4y8m33ea 51 5 the the DT cord-021063-4y8m33ea 51 6 viruses virus NNS cord-021063-4y8m33ea 51 7 currently currently RB cord-021063-4y8m33ea 51 8 being be VBG cord-021063-4y8m33ea 51 9 developed develop VBN cord-021063-4y8m33ea 51 10 as as IN cord-021063-4y8m33ea 51 11 gene gene NN cord-021063-4y8m33ea 51 12 therapy therapy NN cord-021063-4y8m33ea 51 13 vectors vector NNS cord-021063-4y8m33ea 51 14 are be VBP cord-021063-4y8m33ea 51 15 presented present VBN cord-021063-4y8m33ea 51 16 in in IN cord-021063-4y8m33ea 51 17 Table Table NNP cord-021063-4y8m33ea 51 18 2 2 CD cord-021063-4y8m33ea 51 19 . . . cord-021063-4y8m33ea 52 1 Wild wild JJ cord-021063-4y8m33ea 52 2 - - HYPH cord-021063-4y8m33ea 52 3 type type NN cord-021063-4y8m33ea 52 4 retroviruses retrovirus NNS cord-021063-4y8m33ea 52 5 are be VBP cord-021063-4y8m33ea 52 6 contained contain VBN cord-021063-4y8m33ea 52 7 within within IN cord-021063-4y8m33ea 52 8 a a DT cord-021063-4y8m33ea 52 9 lipid lipid NN cord-021063-4y8m33ea 52 10 membrane membrane NN cord-021063-4y8m33ea 52 11 and and CC cord-021063-4y8m33ea 52 12 have have VBP cord-021063-4y8m33ea 52 13 two two CD cord-021063-4y8m33ea 52 14 identical identical JJ cord-021063-4y8m33ea 52 15 copies copy NNS cord-021063-4y8m33ea 52 16 of of IN cord-021063-4y8m33ea 52 17 an an DT cord-021063-4y8m33ea 52 18 RNA RNA NNP cord-021063-4y8m33ea 52 19 genome genome NN cord-021063-4y8m33ea 52 20 . . . cord-021063-4y8m33ea 53 1 After after IN cord-021063-4y8m33ea 53 2 the the DT cord-021063-4y8m33ea 53 3 viral viral JJ cord-021063-4y8m33ea 53 4 particle particle NN cord-021063-4y8m33ea 53 5 's 's POS cord-021063-4y8m33ea 53 6 entry entry NN cord-021063-4y8m33ea 53 7 into into IN cord-021063-4y8m33ea 53 8 the the DT cord-021063-4y8m33ea 53 9 cell cell NN cord-021063-4y8m33ea 53 10 , , , cord-021063-4y8m33ea 53 11 the the DT cord-021063-4y8m33ea 53 12 RNA RNA NNP cord-021063-4y8m33ea 53 13 molecule molecule NN cord-021063-4y8m33ea 53 14 is be VBZ cord-021063-4y8m33ea 53 15 reverse reverse RB cord-021063-4y8m33ea 53 16 - - HYPH cord-021063-4y8m33ea 53 17 transcribed transcribe VBN cord-021063-4y8m33ea 53 18 into into IN cord-021063-4y8m33ea 53 19 a a DT cord-021063-4y8m33ea 53 20 DNA dna NN cord-021063-4y8m33ea 53 21 copy copy NN cord-021063-4y8m33ea 53 22 , , , cord-021063-4y8m33ea 53 23 which which WDT cord-021063-4y8m33ea 53 24 is be VBZ cord-021063-4y8m33ea 53 25 then then RB cord-021063-4y8m33ea 53 26 integrated integrate VBN cord-021063-4y8m33ea 53 27 into into IN cord-021063-4y8m33ea 53 28 the the DT cord-021063-4y8m33ea 53 29 host host NN cord-021063-4y8m33ea 53 30 's 's POS cord-021063-4y8m33ea 53 31 genome genome NN cord-021063-4y8m33ea 53 32 , , , cord-021063-4y8m33ea 53 33 mRNAs mRNAs NNPS cord-021063-4y8m33ea 53 34 for for IN cord-021063-4y8m33ea 53 35 the the DT cord-021063-4y8m33ea 53 36 various various JJ cord-021063-4y8m33ea 53 37 viral viral JJ cord-021063-4y8m33ea 53 38 proteins protein NNS cord-021063-4y8m33ea 53 39 synthesized synthesize VBN cord-021063-4y8m33ea 53 40 during during IN cord-021063-4y8m33ea 53 41 the the DT cord-021063-4y8m33ea 53 42 course course NN cord-021063-4y8m33ea 53 43 of of IN cord-021063-4y8m33ea 53 44 the the DT cord-021063-4y8m33ea 53 45 infection infection NN cord-021063-4y8m33ea 53 46 are be VBP cord-021063-4y8m33ea 53 47 transcribed transcribe VBN cord-021063-4y8m33ea 53 48 from from IN cord-021063-4y8m33ea 53 49 this this DT cord-021063-4y8m33ea 53 50 integrated integrate VBN cord-021063-4y8m33ea 53 51 DNA dna NN cord-021063-4y8m33ea 53 52 . . . cord-021063-4y8m33ea 54 1 The the DT cord-021063-4y8m33ea 54 2 integration integration NN cord-021063-4y8m33ea 54 3 of of IN cord-021063-4y8m33ea 54 4 the the DT cord-021063-4y8m33ea 54 5 retroviral retroviral JJ cord-021063-4y8m33ea 54 6 DNA dna NN cord-021063-4y8m33ea 54 7 genome genome NN cord-021063-4y8m33ea 54 8 into into IN cord-021063-4y8m33ea 54 9 the the DT cord-021063-4y8m33ea 54 10 host host NN cord-021063-4y8m33ea 54 11 genome genome NN cord-021063-4y8m33ea 54 12 forms form VBZ cord-021063-4y8m33ea 54 13 the the DT cord-021063-4y8m33ea 54 14 basis basis NN cord-021063-4y8m33ea 54 15 for for IN cord-021063-4y8m33ea 54 16 the the DT cord-021063-4y8m33ea 54 17 use use NN cord-021063-4y8m33ea 54 18 of of IN cord-021063-4y8m33ea 54 19 retroviruses retrovirus NNS cord-021063-4y8m33ea 54 20 as as IN cord-021063-4y8m33ea 54 21 vectors vector NNS cord-021063-4y8m33ea 54 22 for for IN cord-021063-4y8m33ea 54 23 the the DT cord-021063-4y8m33ea 54 24 introduction introduction NN cord-021063-4y8m33ea 54 25 of of IN cord-021063-4y8m33ea 54 26 exogenous exogenous JJ cord-021063-4y8m33ea 54 27 DNA dna NN cord-021063-4y8m33ea 54 28 into into IN cord-021063-4y8m33ea 54 29 eukaryotic eukaryotic JJ cord-021063-4y8m33ea 54 30 cells cell NNS cord-021063-4y8m33ea 55 1 ( ( -LRB- cord-021063-4y8m33ea 55 2 Hoeben Hoeben NNP cord-021063-4y8m33ea 55 3 et et FW cord-021063-4y8m33ea 55 4 al al NNP cord-021063-4y8m33ea 55 5 . . NNP cord-021063-4y8m33ea 55 6 , , , cord-021063-4y8m33ea 55 7 1992 1992 CD cord-021063-4y8m33ea 55 8 ) ) -RRB- cord-021063-4y8m33ea 55 9 . . . cord-021063-4y8m33ea 56 1 To to TO cord-021063-4y8m33ea 56 2 convert convert VB cord-021063-4y8m33ea 56 3 a a DT cord-021063-4y8m33ea 56 4 wild wild JJ cord-021063-4y8m33ea 56 5 - - HYPH cord-021063-4y8m33ea 56 6 type type NN cord-021063-4y8m33ea 56 7 retrovirus retrovirus NN cord-021063-4y8m33ea 56 8 into into IN cord-021063-4y8m33ea 56 9 a a DT cord-021063-4y8m33ea 56 10 retroviral retroviral JJ cord-021063-4y8m33ea 56 11 gene gene NN cord-021063-4y8m33ea 56 12 therapy therapy NN cord-021063-4y8m33ea 56 13 vector vector NN cord-021063-4y8m33ea 56 14 , , , cord-021063-4y8m33ea 56 15 two two CD cord-021063-4y8m33ea 56 16 steps step NNS cord-021063-4y8m33ea 56 17 are be VBP cord-021063-4y8m33ea 56 18 necessary necessary JJ cord-021063-4y8m33ea 56 19 : : : cord-021063-4y8m33ea 56 20 first first RB cord-021063-4y8m33ea 56 21 , , , cord-021063-4y8m33ea 56 22 the the DT cord-021063-4y8m33ea 56 23 therapeutic therapeutic JJ cord-021063-4y8m33ea 56 24 gene gene NN cord-021063-4y8m33ea 56 25 must must MD cord-021063-4y8m33ea 56 26 be be VB cord-021063-4y8m33ea 56 27 added add VBN cord-021063-4y8m33ea 56 28 to to IN cord-021063-4y8m33ea 56 29 the the DT cord-021063-4y8m33ea 56 30 retroviral retroviral NN cord-021063-4y8m33ea 56 31 and and CC cord-021063-4y8m33ea 56 32 , , , cord-021063-4y8m33ea 56 33 genome genome JJ cord-021063-4y8m33ea 56 34 second second NN cord-021063-4y8m33ea 56 35 , , , cord-021063-4y8m33ea 56 36 the the DT cord-021063-4y8m33ea 56 37 potential potential NN cord-021063-4y8m33ea 56 38 of of IN cord-021063-4y8m33ea 56 39 the the DT cord-021063-4y8m33ea 56 40 retrovirus retrovirus NN cord-021063-4y8m33ea 56 41 to to TO cord-021063-4y8m33ea 56 42 remain remain VB cord-021063-4y8m33ea 56 43 infectious infectious JJ cord-021063-4y8m33ea 56 44 after after IN cord-021063-4y8m33ea 56 45 integration integration NN cord-021063-4y8m33ea 56 46 into into IN cord-021063-4y8m33ea 56 47 the the DT cord-021063-4y8m33ea 56 48 target target NN cord-021063-4y8m33ea 56 49 cell cell NN cord-021063-4y8m33ea 56 50 must must MD cord-021063-4y8m33ea 56 51 be be VB cord-021063-4y8m33ea 56 52 eliminated eliminate VBN cord-021063-4y8m33ea 56 53 . . . cord-021063-4y8m33ea 57 1 Presently presently RB cord-021063-4y8m33ea 57 2 , , , cord-021063-4y8m33ea 57 3 this this DT cord-021063-4y8m33ea 57 4 is be VBZ cord-021063-4y8m33ea 57 5 accomplished accomplish VBN cord-021063-4y8m33ea 57 6 by by IN cord-021063-4y8m33ea 57 7 inserting insert VBG cord-021063-4y8m33ea 57 8 a a DT cord-021063-4y8m33ea 57 9 therapeutic therapeutic JJ cord-021063-4y8m33ea 57 10 gene gene NN cord-021063-4y8m33ea 57 11 into into IN cord-021063-4y8m33ea 57 12 a a DT cord-021063-4y8m33ea 57 13 retroviral retroviral JJ cord-021063-4y8m33ea 57 14 genome genome NN cord-021063-4y8m33ea 57 15 that that WDT cord-021063-4y8m33ea 57 16 has have VBZ cord-021063-4y8m33ea 57 17 had have VBN cord-021063-4y8m33ea 57 18 most most JJS cord-021063-4y8m33ea 57 19 of of IN cord-021063-4y8m33ea 57 20 the the DT cord-021063-4y8m33ea 57 21 genes gene NNS cord-021063-4y8m33ea 57 22 necessary necessary JJ cord-021063-4y8m33ea 57 23 for for IN cord-021063-4y8m33ea 57 24 packaging package VBG cord-021063-4y8m33ea 57 25 the the DT cord-021063-4y8m33ea 57 26 virus virus NN cord-021063-4y8m33ea 57 27 removed remove VBN cord-021063-4y8m33ea 57 28 or or CC cord-021063-4y8m33ea 57 29 mutated mutate VBN cord-021063-4y8m33ea 57 30 . . . cord-021063-4y8m33ea 58 1 Deletion deletion NN cord-021063-4y8m33ea 58 2 of of IN cord-021063-4y8m33ea 58 3 the the DT cord-021063-4y8m33ea 58 4 viral viral JJ cord-021063-4y8m33ea 58 5 genes gene NNS cord-021063-4y8m33ea 58 6 eliminates eliminate VBZ cord-021063-4y8m33ea 58 7 infectivity infectivity NN cord-021063-4y8m33ea 58 8 in in IN cord-021063-4y8m33ea 58 9 the the DT cord-021063-4y8m33ea 58 10 treated treat VBN cord-021063-4y8m33ea 58 11 cells cell NNS cord-021063-4y8m33ea 58 12 by by IN cord-021063-4y8m33ea 58 13 preventing prevent VBG cord-021063-4y8m33ea 58 14 the the DT cord-021063-4y8m33ea 58 15 newly newly RB cord-021063-4y8m33ea 58 16 integrated integrate VBN cord-021063-4y8m33ea 58 17 genome genome NN cord-021063-4y8m33ea 58 18 from from IN cord-021063-4y8m33ea 58 19 making make VBG cord-021063-4y8m33ea 58 20 infectious infectious JJ cord-021063-4y8m33ea 58 21 copies copy NNS cord-021063-4y8m33ea 58 22 of of IN cord-021063-4y8m33ea 58 23 itself -PRON- PRP cord-021063-4y8m33ea 58 24 that that WDT cord-021063-4y8m33ea 58 25 could could MD cord-021063-4y8m33ea 58 26 complete complete VB cord-021063-4y8m33ea 58 27 further further JJ cord-021063-4y8m33ea 58 28 rounds round NNS cord-021063-4y8m33ea 58 29 of of IN cord-021063-4y8m33ea 58 30 infection infection NN cord-021063-4y8m33ea 58 31 . . . cord-021063-4y8m33ea 59 1 It -PRON- PRP cord-021063-4y8m33ea 59 2 also also RB cord-021063-4y8m33ea 59 3 has have VBZ cord-021063-4y8m33ea 59 4 the the DT cord-021063-4y8m33ea 59 5 added add VBN cord-021063-4y8m33ea 59 6 benefit benefit NN cord-021063-4y8m33ea 59 7 of of IN cord-021063-4y8m33ea 59 8 increasing increase VBG cord-021063-4y8m33ea 59 9 the the DT cord-021063-4y8m33ea 59 10 maximum maximum JJ cord-021063-4y8m33ea 59 11 length length NN cord-021063-4y8m33ea 59 12 of of IN cord-021063-4y8m33ea 59 13 a a DT cord-021063-4y8m33ea 59 14 therapeutic therapeutic JJ cord-021063-4y8m33ea 59 15 gene gene NN cord-021063-4y8m33ea 59 16 that that WDT cord-021063-4y8m33ea 59 17 can can MD cord-021063-4y8m33ea 59 18 be be VB cord-021063-4y8m33ea 59 19 delivered deliver VBN cord-021063-4y8m33ea 59 20 by by IN cord-021063-4y8m33ea 59 21 a a DT cord-021063-4y8m33ea 59 22 retrovirus retrovirus NN cord-021063-4y8m33ea 59 23 . . . cord-021063-4y8m33ea 60 1 Some some DT cord-021063-4y8m33ea 60 2 advantages advantage NNS cord-021063-4y8m33ea 60 3 of of IN cord-021063-4y8m33ea 60 4 retroviruses retrovirus NNS cord-021063-4y8m33ea 60 5 as as IN cord-021063-4y8m33ea 60 6 gene gene NN cord-021063-4y8m33ea 60 7 delivery delivery NN cord-021063-4y8m33ea 60 8 vectors vector NNS cord-021063-4y8m33ea 60 9 include include VBP cord-021063-4y8m33ea 60 10 : : : cord-021063-4y8m33ea 60 11 ( ( -LRB- cord-021063-4y8m33ea 60 12 i i NN cord-021063-4y8m33ea 60 13 ) ) -RRB- cord-021063-4y8m33ea 61 1 the the DT cord-021063-4y8m33ea 61 2 efficient efficient JJ cord-021063-4y8m33ea 61 3 and and CC cord-021063-4y8m33ea 61 4 stable stable JJ cord-021063-4y8m33ea 61 5 integration integration NN cord-021063-4y8m33ea 61 6 of of IN cord-021063-4y8m33ea 61 7 the the DT cord-021063-4y8m33ea 61 8 introduced introduce VBN cord-021063-4y8m33ea 61 9 gene gene NN cord-021063-4y8m33ea 61 10 into into IN cord-021063-4y8m33ea 61 11 the the DT cord-021063-4y8m33ea 61 12 host host NN cord-021063-4y8m33ea 61 13 genome genome NN cord-021063-4y8m33ea 61 14 , , , cord-021063-4y8m33ea 61 15 ( ( -LRB- cord-021063-4y8m33ea 61 16 ii ii NN cord-021063-4y8m33ea 61 17 ) ) -RRB- cord-021063-4y8m33ea 61 18 a a DT cord-021063-4y8m33ea 61 19 wide wide JJ cord-021063-4y8m33ea 61 20 host host NN cord-021063-4y8m33ea 61 21 range range NN cord-021063-4y8m33ea 61 22 , , , cord-021063-4y8m33ea 61 23 and and CC cord-021063-4y8m33ea 61 24 ( ( -LRB- cord-021063-4y8m33ea 61 25 iii iii NN cord-021063-4y8m33ea 61 26 ) ) -RRB- cord-021063-4y8m33ea 62 1 the the DT cord-021063-4y8m33ea 62 2 ability ability NN cord-021063-4y8m33ea 62 3 to to TO cord-021063-4y8m33ea 62 4 infect infect VB cord-021063-4y8m33ea 62 5 large large JJ cord-021063-4y8m33ea 62 6 numbers number NNS cord-021063-4y8m33ea 62 7 of of IN cord-021063-4y8m33ea 62 8 cells cell NNS cord-021063-4y8m33ea 62 9 . . . cord-021063-4y8m33ea 63 1 Potential potential JJ cord-021063-4y8m33ea 63 2 problems problem NNS cord-021063-4y8m33ea 63 3 associated associate VBN cord-021063-4y8m33ea 63 4 with with IN cord-021063-4y8m33ea 63 5 the the DT cord-021063-4y8m33ea 63 6 use use NN cord-021063-4y8m33ea 63 7 of of IN cord-021063-4y8m33ea 63 8 viral viral JJ cord-021063-4y8m33ea 63 9 vectors vector NNS cord-021063-4y8m33ea 63 10 include include VBP cord-021063-4y8m33ea 63 11 : : : cord-021063-4y8m33ea 63 12 ( ( -LRB- cord-021063-4y8m33ea 63 13 i i NN cord-021063-4y8m33ea 63 14 ) ) -RRB- cord-021063-4y8m33ea 64 1 the the DT cord-021063-4y8m33ea 64 2 possibility possibility NN cord-021063-4y8m33ea 64 3 of of IN cord-021063-4y8m33ea 64 4 recombination recombination NN cord-021063-4y8m33ea 64 5 events event NNS cord-021063-4y8m33ea 64 6 that that WDT cord-021063-4y8m33ea 64 7 could could MD cord-021063-4y8m33ea 64 8 convert convert VB cord-021063-4y8m33ea 64 9 a a DT cord-021063-4y8m33ea 64 10 replication replication NN cord-021063-4y8m33ea 64 11 - - HYPH cord-021063-4y8m33ea 64 12 defective defective JJ cord-021063-4y8m33ea 64 13 vector vector NN cord-021063-4y8m33ea 64 14 into into IN cord-021063-4y8m33ea 64 15 an an DT cord-021063-4y8m33ea 64 16 infectious infectious JJ cord-021063-4y8m33ea 64 17 agent agent NN cord-021063-4y8m33ea 64 18 , , , cord-021063-4y8m33ea 64 19 ( ( -LRB- cord-021063-4y8m33ea 64 20 ii ii NN cord-021063-4y8m33ea 64 21 ) ) -RRB- cord-021063-4y8m33ea 65 1 the the DT cord-021063-4y8m33ea 65 2 possibility possibility NN cord-021063-4y8m33ea 65 3 that that IN cord-021063-4y8m33ea 65 4 superinfection superinfection NN cord-021063-4y8m33ea 65 5 with with IN cord-021063-4y8m33ea 65 6 another another DT cord-021063-4y8m33ea 65 7 retrovirus retrovirus NN cord-021063-4y8m33ea 65 8 may may MD cord-021063-4y8m33ea 65 9 allow allow VB cord-021063-4y8m33ea 65 10 unwanted unwanted JJ cord-021063-4y8m33ea 65 11 transfer transfer NN cord-021063-4y8m33ea 65 12 of of IN cord-021063-4y8m33ea 65 13 the the DT cord-021063-4y8m33ea 65 14 introduced introduce VBN cord-021063-4y8m33ea 65 15 gene gene NN cord-021063-4y8m33ea 65 16 between between IN cord-021063-4y8m33ea 65 17 individuals individual NNS cord-021063-4y8m33ea 65 18 , , , cord-021063-4y8m33ea 65 19 ( ( -LRB- cord-021063-4y8m33ea 65 20 iii iii NN cord-021063-4y8m33ea 65 21 ) ) -RRB- cord-021063-4y8m33ea 65 22 a a DT cord-021063-4y8m33ea 65 23 7 7 CD cord-021063-4y8m33ea 65 24 - - SYM cord-021063-4y8m33ea 65 25 13 13 CD cord-021063-4y8m33ea 65 26 kb kb NNP cord-021063-4y8m33ea 65 27 limit limit NN cord-021063-4y8m33ea 65 28 on on IN cord-021063-4y8m33ea 65 29 the the DT cord-021063-4y8m33ea 65 30 amount amount NN cord-021063-4y8m33ea 65 31 of of IN cord-021063-4y8m33ea 65 32 DNA dna NN cord-021063-4y8m33ea 65 33 that that WDT cord-021063-4y8m33ea 65 34 can can MD cord-021063-4y8m33ea 65 35 be be VB cord-021063-4y8m33ea 65 36 packaged package VBN cord-021063-4y8m33ea 65 37 , , , cord-021063-4y8m33ea 65 38 ( ( -LRB- cord-021063-4y8m33ea 65 39 iv iv LS cord-021063-4y8m33ea 65 40 ) ) -RRB- cord-021063-4y8m33ea 65 41 potential potential JJ cord-021063-4y8m33ea 65 42 problems problem NNS cord-021063-4y8m33ea 65 43 in in IN cord-021063-4y8m33ea 65 44 targeting target VBG cord-021063-4y8m33ea 65 45 the the DT cord-021063-4y8m33ea 65 46 virus virus NN cord-021063-4y8m33ea 65 47 to to IN cord-021063-4y8m33ea 65 48 specific specific JJ cord-021063-4y8m33ea 65 49 cells cell NNS cord-021063-4y8m33ea 65 50 , , , cord-021063-4y8m33ea 65 51 and and CC cord-021063-4y8m33ea 65 52 ( ( -LRB- cord-021063-4y8m33ea 65 53 v v NN cord-021063-4y8m33ea 65 54 ) ) -RRB- cord-021063-4y8m33ea 65 55 difficulty difficulty NN cord-021063-4y8m33ea 65 56 in in IN cord-021063-4y8m33ea 65 57 maintaining maintain VBG cord-021063-4y8m33ea 65 58 high high JJ cord-021063-4y8m33ea 65 59 - - HYPH cord-021063-4y8m33ea 65 60 level level NN cord-021063-4y8m33ea 65 61 expression expression NN cord-021063-4y8m33ea 65 62 of of IN cord-021063-4y8m33ea 65 63 the the DT cord-021063-4y8m33ea 65 64 exogenous exogenous JJ cord-021063-4y8m33ea 65 65 gene gene NN cord-021063-4y8m33ea 65 66 . . . cord-021063-4y8m33ea 66 1 Wild wild JJ cord-021063-4y8m33ea 66 2 - - HYPH cord-021063-4y8m33ea 66 3 type type NN cord-021063-4y8m33ea 66 4 adenoviruses adenovirus NNS cord-021063-4y8m33ea 66 5 cause cause VBP cord-021063-4y8m33ea 66 6 respiratory respiratory JJ cord-021063-4y8m33ea 66 7 disease disease NN cord-021063-4y8m33ea 66 8 in in IN cord-021063-4y8m33ea 66 9 humans human NNS cord-021063-4y8m33ea 66 10 . . . cord-021063-4y8m33ea 67 1 The the DT cord-021063-4y8m33ea 67 2 adenovirus adenovirus NN cord-021063-4y8m33ea 67 3 genome genome NN cord-021063-4y8m33ea 67 4 is be VBZ cord-021063-4y8m33ea 67 5 a a DT cord-021063-4y8m33ea 67 6 linear linear JJ cord-021063-4y8m33ea 67 7 double double RB cord-021063-4y8m33ea 67 8 - - HYPH cord-021063-4y8m33ea 67 9 stranded strand VBN cord-021063-4y8m33ea 67 10 DNA dna NN cord-021063-4y8m33ea 67 11 molecule molecule NN cord-021063-4y8m33ea 67 12 , , , cord-021063-4y8m33ea 67 13 about about RB cord-021063-4y8m33ea 67 14 36 36 CD cord-021063-4y8m33ea 67 15 kb kb NNS cord-021063-4y8m33ea 67 16 in in IN cord-021063-4y8m33ea 67 17 length length NN cord-021063-4y8m33ea 67 18 . . . cord-021063-4y8m33ea 68 1 Although although IN cord-021063-4y8m33ea 68 2 the the DT cord-021063-4y8m33ea 68 3 virus virus NN cord-021063-4y8m33ea 68 4 does do VBZ cord-021063-4y8m33ea 68 5 not not RB cord-021063-4y8m33ea 68 6 have have VB cord-021063-4y8m33ea 68 7 a a DT cord-021063-4y8m33ea 68 8 lipid lipid NN cord-021063-4y8m33ea 68 9 coat coat NN cord-021063-4y8m33ea 68 10 , , , cord-021063-4y8m33ea 68 11 it -PRON- PRP cord-021063-4y8m33ea 68 12 is be VBZ cord-021063-4y8m33ea 68 13 taken take VBN cord-021063-4y8m33ea 68 14 up up RP cord-021063-4y8m33ea 68 15 by by IN cord-021063-4y8m33ea 68 16 cells cell NNS cord-021063-4y8m33ea 68 17 via via IN cord-021063-4y8m33ea 68 18 endocytosis endocytosis NN cord-021063-4y8m33ea 68 19 and and CC cord-021063-4y8m33ea 68 20 enters enter VBZ cord-021063-4y8m33ea 68 21 the the DT cord-021063-4y8m33ea 68 22 cytoplasm cytoplasm NN cord-021063-4y8m33ea 68 23 in in IN cord-021063-4y8m33ea 68 24 a a DT cord-021063-4y8m33ea 68 25 manner manner NN cord-021063-4y8m33ea 68 26 analogous analogous JJ cord-021063-4y8m33ea 68 27 to to IN cord-021063-4y8m33ea 68 28 the the DT cord-021063-4y8m33ea 68 29 retrovirus retrovirus NN cord-021063-4y8m33ea 68 30 . . . cord-021063-4y8m33ea 69 1 Once once IN cord-021063-4y8m33ea 69 2 inside inside IN cord-021063-4y8m33ea 69 3 the the DT cord-021063-4y8m33ea 69 4 cell cell NN cord-021063-4y8m33ea 69 5 , , , cord-021063-4y8m33ea 69 6 the the DT cord-021063-4y8m33ea 69 7 viral viral JJ cord-021063-4y8m33ea 69 8 DNA dna NN cord-021063-4y8m33ea 69 9 moves move NNS cord-021063-4y8m33ea 69 10 to to IN cord-021063-4y8m33ea 69 11 the the DT cord-021063-4y8m33ea 69 12 nucleus nucleus NN cord-021063-4y8m33ea 69 13 and and CC cord-021063-4y8m33ea 69 14 begins begin VBZ cord-021063-4y8m33ea 69 15 its -PRON- PRP$ cord-021063-4y8m33ea 69 16 replication replication NN cord-021063-4y8m33ea 69 17 cycle cycle NN cord-021063-4y8m33ea 69 18 without without IN cord-021063-4y8m33ea 69 19 becoming become VBG cord-021063-4y8m33ea 69 20 part part NN cord-021063-4y8m33ea 69 21 of of IN cord-021063-4y8m33ea 69 22 the the DT cord-021063-4y8m33ea 69 23 host host NN cord-021063-4y8m33ea 69 24 cell cell NN cord-021063-4y8m33ea 69 25 's 's POS cord-021063-4y8m33ea 69 26 genome genome NN cord-021063-4y8m33ea 69 27 . . . cord-021063-4y8m33ea 70 1 Adenoviruses adenovirus NNS cord-021063-4y8m33ea 70 2 that that WDT cord-021063-4y8m33ea 70 3 are be VBP cord-021063-4y8m33ea 70 4 being be VBG cord-021063-4y8m33ea 70 5 considered consider VBN cord-021063-4y8m33ea 70 6 for for IN cord-021063-4y8m33ea 70 7 use use NN cord-021063-4y8m33ea 70 8 as as IN cord-021063-4y8m33ea 70 9 gene gene NN cord-021063-4y8m33ea 70 10 therapy therapy NN cord-021063-4y8m33ea 70 11 vectors vector NNS cord-021063-4y8m33ea 70 12 have have VBP cord-021063-4y8m33ea 70 13 had have VBN cord-021063-4y8m33ea 70 14 substantial substantial JJ cord-021063-4y8m33ea 70 15 parts part NNS cord-021063-4y8m33ea 70 16 of of IN cord-021063-4y8m33ea 70 17 their -PRON- PRP$ cord-021063-4y8m33ea 70 18 genome genome NN cord-021063-4y8m33ea 70 19 removed remove VBN cord-021063-4y8m33ea 70 20 , , , cord-021063-4y8m33ea 70 21 rendering render VBG cord-021063-4y8m33ea 70 22 them -PRON- PRP cord-021063-4y8m33ea 70 23 unable unable JJ cord-021063-4y8m33ea 70 24 to to TO cord-021063-4y8m33ea 70 25 replicate replicate VB cord-021063-4y8m33ea 70 26 except except IN cord-021063-4y8m33ea 70 27 in in IN cord-021063-4y8m33ea 70 28 specially specially RB cord-021063-4y8m33ea 70 29 developed develop VBN cord-021063-4y8m33ea 70 30 cell cell NN cord-021063-4y8m33ea 70 31 lines line NNS cord-021063-4y8m33ea 70 32 ( ( -LRB- cord-021063-4y8m33ea 70 33 i.e. i.e. FW cord-021063-4y8m33ea 70 34 , , , cord-021063-4y8m33ea 70 35 packaging packaging NN cord-021063-4y8m33ea 70 36 cell cell NN cord-021063-4y8m33ea 70 37 lines line NNS cord-021063-4y8m33ea 70 38 ) ) -RRB- cord-021063-4y8m33ea 70 39 that that WDT cord-021063-4y8m33ea 70 40 express express VBP cord-021063-4y8m33ea 70 41 the the DT cord-021063-4y8m33ea 70 42 removed remove VBN cord-021063-4y8m33ea 70 43 proteins protein NNS cord-021063-4y8m33ea 70 44 ( ( -LRB- cord-021063-4y8m33ea 70 45 Kozarsky Kozarsky NNP cord-021063-4y8m33ea 70 46 and and CC cord-021063-4y8m33ea 70 47 Wilson Wilson NNP cord-021063-4y8m33ea 70 48 , , , cord-021063-4y8m33ea 70 49 1993 1993 CD cord-021063-4y8m33ea 70 50 ) ) -RRB- cord-021063-4y8m33ea 70 51 . . . cord-021063-4y8m33ea 71 1 The the DT cord-021063-4y8m33ea 71 2 therapeutic therapeutic JJ cord-021063-4y8m33ea 71 3 gene gene NN cord-021063-4y8m33ea 71 4 to to TO cord-021063-4y8m33ea 71 5 be be VB cord-021063-4y8m33ea 71 6 introduced introduce VBN cord-021063-4y8m33ea 71 7 is be VBZ cord-021063-4y8m33ea 71 8 added add VBN cord-021063-4y8m33ea 71 9 to to IN cord-021063-4y8m33ea 71 10 the the DT cord-021063-4y8m33ea 71 11 adenoviral adenoviral JJ cord-021063-4y8m33ea 71 12 genome genome NN cord-021063-4y8m33ea 71 13 by by IN cord-021063-4y8m33ea 71 14 homologous homologous JJ cord-021063-4y8m33ea 71 15 recombination recombination NN cord-021063-4y8m33ea 71 16 with with IN cord-021063-4y8m33ea 71 17 a a DT cord-021063-4y8m33ea 71 18 plasmid plasmid NN cord-021063-4y8m33ea 71 19 containing contain VBG cord-021063-4y8m33ea 71 20 the the DT cord-021063-4y8m33ea 71 21 therapeutic therapeutic JJ cord-021063-4y8m33ea 71 22 gene gene NN cord-021063-4y8m33ea 71 23 flanked flank VBN cord-021063-4y8m33ea 71 24 by by IN cord-021063-4y8m33ea 71 25 adenoviral adenoviral NNP cord-021063-4y8m33ea 71 26 DNA DNA NNP cord-021063-4y8m33ea 71 27 . . . cord-021063-4y8m33ea 72 1 Although although IN cord-021063-4y8m33ea 72 2 possible possible JJ cord-021063-4y8m33ea 72 3 target target NN cord-021063-4y8m33ea 72 4 organs organ NNS cord-021063-4y8m33ea 72 5 for for IN cord-021063-4y8m33ea 72 6 adenoviral adenoviral JJ cord-021063-4y8m33ea 72 7 gene gene NN cord-021063-4y8m33ea 72 8 therapy therapy NN cord-021063-4y8m33ea 72 9 include include VBP cord-021063-4y8m33ea 72 10 liver liver NN cord-021063-4y8m33ea 72 11 , , , cord-021063-4y8m33ea 72 12 central central JJ cord-021063-4y8m33ea 72 13 nervous nervous JJ cord-021063-4y8m33ea 72 14 system system NN cord-021063-4y8m33ea 72 15 , , , cord-021063-4y8m33ea 72 16 vascular vascular JJ cord-021063-4y8m33ea 72 17 endothelium endothelium NN cord-021063-4y8m33ea 72 18 , , , cord-021063-4y8m33ea 72 19 and and CC cord-021063-4y8m33ea 72 20 muscle muscle NN cord-021063-4y8m33ea 72 21 , , , cord-021063-4y8m33ea 72 22 the the DT cord-021063-4y8m33ea 72 23 primary primary JJ cord-021063-4y8m33ea 72 24 target target NN cord-021063-4y8m33ea 72 25 organ organ NN cord-021063-4y8m33ea 72 26 is be VBZ cord-021063-4y8m33ea 72 27 the the DT cord-021063-4y8m33ea 72 28 lung lung NN cord-021063-4y8m33ea 72 29 . . . cord-021063-4y8m33ea 73 1 Clinical clinical JJ cord-021063-4y8m33ea 73 2 trials trial NNS cord-021063-4y8m33ea 73 3 of of IN cord-021063-4y8m33ea 73 4 adenoviral adenoviral JJ cord-021063-4y8m33ea 73 5 gene gene NN cord-021063-4y8m33ea 73 6 therapy therapy NN cord-021063-4y8m33ea 73 7 for for IN cord-021063-4y8m33ea 73 8 treatment treatment NN cord-021063-4y8m33ea 73 9 of of IN cord-021063-4y8m33ea 73 10 ~l ~l NNP cord-021063-4y8m33ea 73 11 - - HYPH cord-021063-4y8m33ea 73 12 antitrypsin antitrypsin NN cord-021063-4y8m33ea 73 13 deficiency deficiency NN cord-021063-4y8m33ea 73 14 and and CC cord-021063-4y8m33ea 73 15 cystic cystic JJ cord-021063-4y8m33ea 73 16 fibrosis fibrosis NN cord-021063-4y8m33ea 73 17 are be VBP cord-021063-4y8m33ea 73 18 underway underway JJ cord-021063-4y8m33ea 73 19 ( ( -LRB- cord-021063-4y8m33ea 73 20 Crystal Crystal NNP cord-021063-4y8m33ea 73 21 , , , cord-021063-4y8m33ea 73 22 1992 1992 CD cord-021063-4y8m33ea 73 23 ) ) -RRB- cord-021063-4y8m33ea 73 24 . . . cord-021063-4y8m33ea 74 1 Advantages advantage NNS cord-021063-4y8m33ea 74 2 of of IN cord-021063-4y8m33ea 74 3 adenovirus adenovirus NN cord-021063-4y8m33ea 74 4 - - HYPH cord-021063-4y8m33ea 74 5 based base VBN cord-021063-4y8m33ea 74 6 vectors vector NNS cord-021063-4y8m33ea 74 7 include include VBP cord-021063-4y8m33ea 74 8 : : : cord-021063-4y8m33ea 74 9 ( ( -LRB- cord-021063-4y8m33ea 74 10 i i NN cord-021063-4y8m33ea 74 11 ) ) -RRB- cord-021063-4y8m33ea 75 1 the the DT cord-021063-4y8m33ea 75 2 ability ability NN cord-021063-4y8m33ea 75 3 to to TO cord-021063-4y8m33ea 75 4 infect infect VB cord-021063-4y8m33ea 75 5 large large JJ cord-021063-4y8m33ea 75 6 numbers number NNS cord-021063-4y8m33ea 75 7 of of IN cord-021063-4y8m33ea 75 8 cells cell NNS cord-021063-4y8m33ea 75 9 , , , cord-021063-4y8m33ea 75 10 ( ( -LRB- cord-021063-4y8m33ea 75 11 ii ii NN cord-021063-4y8m33ea 75 12 ) ) -RRB- cord-021063-4y8m33ea 75 13 relative relative JJ cord-021063-4y8m33ea 75 14 ease ease NN cord-021063-4y8m33ea 75 15 of of IN cord-021063-4y8m33ea 75 16 constructing construct VBG cord-021063-4y8m33ea 75 17 the the DT cord-021063-4y8m33ea 75 18 vector vector NN cord-021063-4y8m33ea 75 19 and and CC cord-021063-4y8m33ea 75 20 obtaining obtain VBG cord-021063-4y8m33ea 75 21 large large JJ cord-021063-4y8m33ea 75 22 amounts amount NNS cord-021063-4y8m33ea 75 23 of of IN cord-021063-4y8m33ea 75 24 virus virus NN cord-021063-4y8m33ea 75 25 , , , cord-021063-4y8m33ea 75 26 and and CC cord-021063-4y8m33ea 75 27 ( ( -LRB- cord-021063-4y8m33ea 75 28 iii iii NN cord-021063-4y8m33ea 75 29 ) ) -RRB- cord-021063-4y8m33ea 75 30 absence absence NN cord-021063-4y8m33ea 75 31 of of IN cord-021063-4y8m33ea 75 32 genomic genomic JJ cord-021063-4y8m33ea 75 33 integration integration NN cord-021063-4y8m33ea 75 34 , , , cord-021063-4y8m33ea 75 35 obviating obviate VBG cord-021063-4y8m33ea 75 36 the the DT cord-021063-4y8m33ea 75 37 problem problem NN cord-021063-4y8m33ea 75 38 of of IN cord-021063-4y8m33ea 75 39 insertional insertional JJ cord-021063-4y8m33ea 75 40 mutagenesis mutagenesis NN cord-021063-4y8m33ea 75 41 . . . cord-021063-4y8m33ea 76 1 Some some DT cord-021063-4y8m33ea 76 2 disadvantages disadvantage NNS cord-021063-4y8m33ea 76 3 are be VBP cord-021063-4y8m33ea 76 4 : : : cord-021063-4y8m33ea 76 5 ( ( -LRB- cord-021063-4y8m33ea 76 6 i i NN cord-021063-4y8m33ea 76 7 ) ) -RRB- cord-021063-4y8m33ea 77 1 the the DT cord-021063-4y8m33ea 77 2 necessity necessity NN cord-021063-4y8m33ea 77 3 to to TO cord-021063-4y8m33ea 77 4 periodically periodically RB cord-021063-4y8m33ea 77 5 reinfect reinfect VB cord-021063-4y8m33ea 77 6 the the DT cord-021063-4y8m33ea 77 7 patient patient NN cord-021063-4y8m33ea 77 8 , , , cord-021063-4y8m33ea 77 9 as as IN cord-021063-4y8m33ea 77 10 the the DT cord-021063-4y8m33ea 77 11 genome genome NN cord-021063-4y8m33ea 77 12 is be VBZ cord-021063-4y8m33ea 77 13 lost lose VBN cord-021063-4y8m33ea 77 14 from from IN cord-021063-4y8m33ea 77 15 dividing divide VBG cord-021063-4y8m33ea 77 16 cells cell NNS cord-021063-4y8m33ea 77 17 ; ; , cord-021063-4y8m33ea 77 18 ( ( -LRB- cord-021063-4y8m33ea 77 19 ii ii NN cord-021063-4y8m33ea 77 20 ) ) -RRB- cord-021063-4y8m33ea 78 1 the the DT cord-021063-4y8m33ea 78 2 concomitant concomitant JJ cord-021063-4y8m33ea 78 3 development development NN cord-021063-4y8m33ea 78 4 of of IN cord-021063-4y8m33ea 78 5 an an DT cord-021063-4y8m33ea 78 6 allergic allergic JJ cord-021063-4y8m33ea 78 7 response response NN cord-021063-4y8m33ea 78 8 ; ; : cord-021063-4y8m33ea 78 9 and and CC cord-021063-4y8m33ea 78 10 ( ( -LRB- cord-021063-4y8m33ea 78 11 iii iii NN cord-021063-4y8m33ea 78 12 ) ) -RRB- cord-021063-4y8m33ea 79 1 possible possible JJ cord-021063-4y8m33ea 79 2 toxicity toxicity NN cord-021063-4y8m33ea 79 3 of of IN cord-021063-4y8m33ea 79 4 high high JJ cord-021063-4y8m33ea 79 5 doses dose NNS cord-021063-4y8m33ea 79 6 of of IN cord-021063-4y8m33ea 79 7 virus virus NN cord-021063-4y8m33ea 79 8 . . . cord-021063-4y8m33ea 80 1 Adeno Adeno NNP cord-021063-4y8m33ea 80 2 - - HYPH cord-021063-4y8m33ea 80 3 associated associate VBN cord-021063-4y8m33ea 80 4 virus virus NN cord-021063-4y8m33ea 80 5 is be VBZ cord-021063-4y8m33ea 80 6 a a DT cord-021063-4y8m33ea 80 7 naturally naturally RB cord-021063-4y8m33ea 80 8 occurring occur VBG cord-021063-4y8m33ea 80 9 defective defective JJ cord-021063-4y8m33ea 80 10 virus virus NN cord-021063-4y8m33ea 80 11 that that WDT cord-021063-4y8m33ea 80 12 infects infect VBZ cord-021063-4y8m33ea 80 13 human human JJ cord-021063-4y8m33ea 80 14 lungs lung NNS cord-021063-4y8m33ea 80 15 . . . cord-021063-4y8m33ea 81 1 Although although IN cord-021063-4y8m33ea 81 2 it -PRON- PRP cord-021063-4y8m33ea 81 3 is be VBZ cord-021063-4y8m33ea 81 4 unable unable JJ cord-021063-4y8m33ea 81 5 to to TO cord-021063-4y8m33ea 81 6 go go VB cord-021063-4y8m33ea 81 7 through through IN cord-021063-4y8m33ea 81 8 lytic lytic JJ cord-021063-4y8m33ea 81 9 infection infection NN cord-021063-4y8m33ea 81 10 of of IN cord-021063-4y8m33ea 81 11 cells cell NNS cord-021063-4y8m33ea 81 12 independently independently RB cord-021063-4y8m33ea 81 13 , , , cord-021063-4y8m33ea 81 14 it -PRON- PRP cord-021063-4y8m33ea 81 15 can can MD cord-021063-4y8m33ea 81 16 do do VB cord-021063-4y8m33ea 81 17 so so RB cord-021063-4y8m33ea 81 18 in in IN cord-021063-4y8m33ea 81 19 the the DT cord-021063-4y8m33ea 81 20 presence presence NN cord-021063-4y8m33ea 81 21 of of IN cord-021063-4y8m33ea 81 22 a a DT cord-021063-4y8m33ea 81 23 separate separate JJ cord-021063-4y8m33ea 81 24 infection infection NN cord-021063-4y8m33ea 81 25 by by IN cord-021063-4y8m33ea 81 26 adenovirus adenovirus NN cord-021063-4y8m33ea 81 27 or or CC cord-021063-4y8m33ea 81 28 herpes herpes NN cord-021063-4y8m33ea 81 29 simplex simplex NN cord-021063-4y8m33ea 81 30 virus virus NN cord-021063-4y8m33ea 81 31 . . . cord-021063-4y8m33ea 82 1 In in IN cord-021063-4y8m33ea 82 2 the the DT cord-021063-4y8m33ea 82 3 absence absence NN cord-021063-4y8m33ea 82 4 of of IN cord-021063-4y8m33ea 82 5 a a DT cord-021063-4y8m33ea 82 6 helper helper NN cord-021063-4y8m33ea 82 7 infection infection NN cord-021063-4y8m33ea 82 8 by by IN cord-021063-4y8m33ea 82 9 one one CD cord-021063-4y8m33ea 82 10 of of IN cord-021063-4y8m33ea 82 11 these these DT cord-021063-4y8m33ea 82 12 viruses virus NNS cord-021063-4y8m33ea 82 13 , , , cord-021063-4y8m33ea 82 14 the the DT cord-021063-4y8m33ea 82 15 adeno adeno NN cord-021063-4y8m33ea 82 16 - - HYPH cord-021063-4y8m33ea 82 17 associated associate VBN cord-021063-4y8m33ea 82 18 virus virus NN cord-021063-4y8m33ea 82 19 establishes establish VBZ cord-021063-4y8m33ea 82 20 a a DT cord-021063-4y8m33ea 82 21 latent latent JJ cord-021063-4y8m33ea 82 22 infection infection NN cord-021063-4y8m33ea 82 23 of of IN cord-021063-4y8m33ea 82 24 the the DT cord-021063-4y8m33ea 82 25 host host NN cord-021063-4y8m33ea 82 26 cell cell NN cord-021063-4y8m33ea 82 27 by by IN cord-021063-4y8m33ea 82 28 integrating integrate VBG cord-021063-4y8m33ea 82 29 itself -PRON- PRP cord-021063-4y8m33ea 82 30 into into IN cord-021063-4y8m33ea 82 31 the the DT cord-021063-4y8m33ea 82 32 host host NN cord-021063-4y8m33ea 82 33 genome genome NN cord-021063-4y8m33ea 82 34 . . . cord-021063-4y8m33ea 83 1 About about RB cord-021063-4y8m33ea 83 2 70 70 CD cord-021063-4y8m33ea 83 3 % % NN cord-021063-4y8m33ea 83 4 of of IN cord-021063-4y8m33ea 83 5 the the DT cord-021063-4y8m33ea 83 6 integrations integration NNS cord-021063-4y8m33ea 83 7 of of IN cord-021063-4y8m33ea 83 8 the the DT cord-021063-4y8m33ea 83 9 wild wild JJ cord-021063-4y8m33ea 83 10 - - HYPH cord-021063-4y8m33ea 83 11 type type NN cord-021063-4y8m33ea 83 12 virus virus NN cord-021063-4y8m33ea 83 13 occur occur VBP cord-021063-4y8m33ea 83 14 at at IN cord-021063-4y8m33ea 83 15 a a DT cord-021063-4y8m33ea 83 16 single single JJ cord-021063-4y8m33ea 83 17 site site NN cord-021063-4y8m33ea 83 18 on on IN cord-021063-4y8m33ea 83 19 chromosome chromosome NN cord-021063-4y8m33ea 83 20 19 19 CD cord-021063-4y8m33ea 84 1 ( ( -LRB- cord-021063-4y8m33ea 84 2 Samulski Samulski NNP cord-021063-4y8m33ea 84 3 et et NNP cord-021063-4y8m33ea 84 4 al al NNP cord-021063-4y8m33ea 84 5 . . NNP cord-021063-4y8m33ea 84 6 , , , cord-021063-4y8m33ea 84 7 1991 1991 CD cord-021063-4y8m33ea 84 8 ) ) -RRB- cord-021063-4y8m33ea 84 9 . . . cord-021063-4y8m33ea 85 1 Because because IN cord-021063-4y8m33ea 85 2 these these DT cord-021063-4y8m33ea 85 3 integrations integration NNS cord-021063-4y8m33ea 85 4 do do VBP cord-021063-4y8m33ea 85 5 not not RB cord-021063-4y8m33ea 85 6 seem seem VB cord-021063-4y8m33ea 85 7 to to TO cord-021063-4y8m33ea 85 8 be be VB cord-021063-4y8m33ea 85 9 associated associate VBN cord-021063-4y8m33ea 85 10 with with IN cord-021063-4y8m33ea 85 11 any any DT cord-021063-4y8m33ea 85 12 disease disease NN cord-021063-4y8m33ea 85 13 , , , cord-021063-4y8m33ea 85 14 this this DT cord-021063-4y8m33ea 85 15 virus virus NN cord-021063-4y8m33ea 85 16 may may MD cord-021063-4y8m33ea 85 17 eventually eventually RB cord-021063-4y8m33ea 85 18 be be VB cord-021063-4y8m33ea 85 19 used use VBN cord-021063-4y8m33ea 85 20 to to TO cord-021063-4y8m33ea 85 21 add add VB cord-021063-4y8m33ea 85 22 therapeutic therapeutic JJ cord-021063-4y8m33ea 85 23 genes gene NNS cord-021063-4y8m33ea 85 24 to to IN cord-021063-4y8m33ea 85 25 the the DT cord-021063-4y8m33ea 85 26 human human JJ cord-021063-4y8m33ea 85 27 genome genome NN cord-021063-4y8m33ea 85 28 with with IN cord-021063-4y8m33ea 85 29 a a DT cord-021063-4y8m33ea 85 30 lower low JJR cord-021063-4y8m33ea 85 31 risk risk NN cord-021063-4y8m33ea 85 32 of of IN cord-021063-4y8m33ea 85 33 insertional insertional JJ cord-021063-4y8m33ea 85 34 mutagenesis mutagenesis NN cord-021063-4y8m33ea 85 35 . . . cord-021063-4y8m33ea 86 1 To to IN cord-021063-4y8m33ea 86 2 date date NN cord-021063-4y8m33ea 86 3 , , , cord-021063-4y8m33ea 86 4 however however RB cord-021063-4y8m33ea 86 5 , , , cord-021063-4y8m33ea 86 6 the the DT cord-021063-4y8m33ea 86 7 targeted targeted JJ cord-021063-4y8m33ea 86 8 nature nature NN cord-021063-4y8m33ea 86 9 of of IN cord-021063-4y8m33ea 86 10 the the DT cord-021063-4y8m33ea 86 11 insertional insertional JJ cord-021063-4y8m33ea 86 12 events event NNS cord-021063-4y8m33ea 86 13 is be VBZ cord-021063-4y8m33ea 86 14 not not RB cord-021063-4y8m33ea 86 15 retained retain VBN cord-021063-4y8m33ea 86 16 when when WRB cord-021063-4y8m33ea 86 17 the the DT cord-021063-4y8m33ea 86 18 native native JJ cord-021063-4y8m33ea 86 19 viral viral JJ cord-021063-4y8m33ea 86 20 genome genome NN cord-021063-4y8m33ea 86 21 is be VBZ cord-021063-4y8m33ea 86 22 replaced replace VBN cord-021063-4y8m33ea 86 23 by by IN cord-021063-4y8m33ea 86 24 a a DT cord-021063-4y8m33ea 86 25 therapeutic therapeutic JJ cord-021063-4y8m33ea 86 26 or or CC cord-021063-4y8m33ea 86 27 marker marker NN cord-021063-4y8m33ea 86 28 gene gene NN cord-021063-4y8m33ea 86 29 . . . cord-021063-4y8m33ea 87 1 In in IN cord-021063-4y8m33ea 87 2 addition addition NN cord-021063-4y8m33ea 87 3 , , , cord-021063-4y8m33ea 87 4 packaging packaging NN cord-021063-4y8m33ea 87 5 constraints constraint NNS cord-021063-4y8m33ea 87 6 limit limit VBP cord-021063-4y8m33ea 87 7 the the DT cord-021063-4y8m33ea 87 8 size size NN cord-021063-4y8m33ea 87 9 of of IN cord-021063-4y8m33ea 87 10 any any DT cord-021063-4y8m33ea 87 11 insert insert NN cord-021063-4y8m33ea 87 12 to to IN cord-021063-4y8m33ea 87 13 4.5 4.5 CD cord-021063-4y8m33ea 87 14 - - SYM cord-021063-4y8m33ea 87 15 5 5 CD cord-021063-4y8m33ea 87 16 kb kb NNP cord-021063-4y8m33ea 87 17 of of IN cord-021063-4y8m33ea 87 18 DNA DNA NNP cord-021063-4y8m33ea 87 19 . . . cord-021063-4y8m33ea 88 1 The the DT cord-021063-4y8m33ea 88 2 genomes genome NNS cord-021063-4y8m33ea 88 3 of of IN cord-021063-4y8m33ea 88 4 herpesviruses herpesviruse NNS cord-021063-4y8m33ea 88 5 are be VBP cord-021063-4y8m33ea 88 6 very very RB cord-021063-4y8m33ea 88 7 large large JJ cord-021063-4y8m33ea 88 8 and and CC cord-021063-4y8m33ea 88 9 complex complex JJ cord-021063-4y8m33ea 88 10 . . . cord-021063-4y8m33ea 89 1 This this DT cord-021063-4y8m33ea 89 2 fact fact NN cord-021063-4y8m33ea 89 3 alone alone RB cord-021063-4y8m33ea 89 4 might may MD cord-021063-4y8m33ea 89 5 argue argue VB cord-021063-4y8m33ea 89 6 against against IN cord-021063-4y8m33ea 89 7 the the DT cord-021063-4y8m33ea 89 8 use use NN cord-021063-4y8m33ea 89 9 of of IN cord-021063-4y8m33ea 89 10 herpes herpes NNP cord-021063-4y8m33ea 89 11 simplex simplex NNP cord-021063-4y8m33ea 89 12 virus virus NN cord-021063-4y8m33ea 90 1 I -PRON- PRP cord-021063-4y8m33ea 90 2 ( ( -LRB- cord-021063-4y8m33ea 90 3 HSV HSV NNP cord-021063-4y8m33ea 90 4 - - HYPH cord-021063-4y8m33ea 90 5 I I NNP cord-021063-4y8m33ea 90 6 ) ) -RRB- cord-021063-4y8m33ea 90 7 as as IN cord-021063-4y8m33ea 90 8 a a DT cord-021063-4y8m33ea 90 9 gene gene NN cord-021063-4y8m33ea 90 10 therapy therapy NN cord-021063-4y8m33ea 90 11 vector vector NN cord-021063-4y8m33ea 90 12 , , , cord-021063-4y8m33ea 90 13 since since IN cord-021063-4y8m33ea 90 14 a a DT cord-021063-4y8m33ea 90 15 complex complex JJ cord-021063-4y8m33ea 90 16 genome genome NN cord-021063-4y8m33ea 90 17 will will MD cord-021063-4y8m33ea 90 18 be be VB cord-021063-4y8m33ea 90 19 more more RBR cord-021063-4y8m33ea 90 20 difficult difficult JJ cord-021063-4y8m33ea 90 21 to to TO cord-021063-4y8m33ea 90 22 effectively effectively RB cord-021063-4y8m33ea 90 23 " " `` cord-021063-4y8m33ea 90 24 tame tame JJ cord-021063-4y8m33ea 90 25 . . . cord-021063-4y8m33ea 90 26 " " '' cord-021063-4y8m33ea 91 1 However however RB cord-021063-4y8m33ea 91 2 , , , cord-021063-4y8m33ea 91 3 HSV HSV NNP cord-021063-4y8m33ea 91 4 - - HYPH cord-021063-4y8m33ea 91 5 I -PRON- PRP cord-021063-4y8m33ea 91 6 has have VBZ cord-021063-4y8m33ea 91 7 an an DT cord-021063-4y8m33ea 91 8 advantage advantage NN cord-021063-4y8m33ea 91 9 that that WDT cord-021063-4y8m33ea 91 10 compensates compensate VBZ cord-021063-4y8m33ea 91 11 for for IN cord-021063-4y8m33ea 91 12 this this DT cord-021063-4y8m33ea 91 13 problem problem NN cord-021063-4y8m33ea 91 14 , , , cord-021063-4y8m33ea 91 15 in in IN cord-021063-4y8m33ea 91 16 that that IN cord-021063-4y8m33ea 91 17 the the DT cord-021063-4y8m33ea 91 18 virus virus NN cord-021063-4y8m33ea 91 19 can can MD cord-021063-4y8m33ea 91 20 exist exist VB cord-021063-4y8m33ea 91 21 and and CC cord-021063-4y8m33ea 91 22 mediate mediate VB cord-021063-4y8m33ea 91 23 persistent persistent JJ cord-021063-4y8m33ea 91 24 expression expression NN cord-021063-4y8m33ea 91 25 of of IN cord-021063-4y8m33ea 91 26 its -PRON- PRP$ cord-021063-4y8m33ea 91 27 genes gene NNS cord-021063-4y8m33ea 91 28 in in IN cord-021063-4y8m33ea 91 29 neurons neuron NNS cord-021063-4y8m33ea 91 30 and and CC cord-021063-4y8m33ea 91 31 other other JJ cord-021063-4y8m33ea 91 32 postmitotic postmitotic JJ cord-021063-4y8m33ea 91 33 cells cell NNS cord-021063-4y8m33ea 91 34 ( ( -LRB- cord-021063-4y8m33ea 91 35 Geller Geller NNP cord-021063-4y8m33ea 91 36 , , , cord-021063-4y8m33ea 91 37 1993 1993 CD cord-021063-4y8m33ea 91 38 ) ) -RRB- cord-021063-4y8m33ea 91 39 . . . cord-021063-4y8m33ea 92 1 In in IN cord-021063-4y8m33ea 92 2 the the DT cord-021063-4y8m33ea 92 3 normal normal JJ cord-021063-4y8m33ea 92 4 course course NN cord-021063-4y8m33ea 92 5 of of IN cord-021063-4y8m33ea 92 6 an an DT cord-021063-4y8m33ea 92 7 infection infection NN cord-021063-4y8m33ea 92 8 , , , cord-021063-4y8m33ea 92 9 HSV HSV NNP cord-021063-4y8m33ea 92 10 - - : cord-021063-4y8m33ea 92 11 I -PRON- PRP cord-021063-4y8m33ea 92 12 will will MD cord-021063-4y8m33ea 92 13 enter enter VB cord-021063-4y8m33ea 92 14 neuronal neuronal JJ cord-021063-4y8m33ea 92 15 cells cell NNS cord-021063-4y8m33ea 92 16 and and CC cord-021063-4y8m33ea 92 17 remain remain VBP cord-021063-4y8m33ea 92 18 latent latent JJ cord-021063-4y8m33ea 92 19 , , , cord-021063-4y8m33ea 92 20 sometimes sometimes RB cord-021063-4y8m33ea 92 21 for for IN cord-021063-4y8m33ea 92 22 years year NNS cord-021063-4y8m33ea 92 23 , , , cord-021063-4y8m33ea 92 24 before before IN cord-021063-4y8m33ea 92 25 reactivating reactivate VBG cord-021063-4y8m33ea 92 26 and and CC cord-021063-4y8m33ea 92 27 starting start VBG cord-021063-4y8m33ea 92 28 a a DT cord-021063-4y8m33ea 92 29 lytic lytic JJ cord-021063-4y8m33ea 92 30 cycle cycle NN cord-021063-4y8m33ea 92 31 that that WDT cord-021063-4y8m33ea 92 32 results result VBZ cord-021063-4y8m33ea 92 33 in in IN cord-021063-4y8m33ea 92 34 a a DT cord-021063-4y8m33ea 92 35 small small JJ cord-021063-4y8m33ea 92 36 patch patch NN cord-021063-4y8m33ea 92 37 of of IN cord-021063-4y8m33ea 92 38 endothelial endothelial JJ cord-021063-4y8m33ea 92 39 cell cell NN cord-021063-4y8m33ea 92 40 death death NN cord-021063-4y8m33ea 92 41 ( ( -LRB- cord-021063-4y8m33ea 92 42 e.g. e.g. RB cord-021063-4y8m33ea 92 43 , , , cord-021063-4y8m33ea 92 44 a a DT cord-021063-4y8m33ea 92 45 cold cold JJ cord-021063-4y8m33ea 92 46 sore sore NN cord-021063-4y8m33ea 92 47 ) ) -RRB- cord-021063-4y8m33ea 92 48 . . . cord-021063-4y8m33ea 93 1 During during IN cord-021063-4y8m33ea 93 2 latency latency NNP cord-021063-4y8m33ea 93 3 , , , cord-021063-4y8m33ea 93 4 the the DT cord-021063-4y8m33ea 93 5 host host NN cord-021063-4y8m33ea 93 6 cell cell NN cord-021063-4y8m33ea 93 7 transcribes transcribe VBZ cord-021063-4y8m33ea 93 8 some some DT cord-021063-4y8m33ea 93 9 viral viral JJ cord-021063-4y8m33ea 93 10 genes gene NNS cord-021063-4y8m33ea 93 11 , , , cord-021063-4y8m33ea 93 12 producing produce VBG cord-021063-4y8m33ea 93 13 what what WP cord-021063-4y8m33ea 93 14 are be VBP cord-021063-4y8m33ea 93 15 termed term VBN cord-021063-4y8m33ea 93 16 latency latency NN cord-021063-4y8m33ea 93 17 associated associate VBN cord-021063-4y8m33ea 93 18 transcripts transcript NNS cord-021063-4y8m33ea 93 19 ( ( -LRB- cord-021063-4y8m33ea 93 20 LATs LATs NNP cord-021063-4y8m33ea 93 21 ) ) -RRB- cord-021063-4y8m33ea 93 22 . . . cord-021063-4y8m33ea 94 1 HSV HSV NNP cord-021063-4y8m33ea 94 2 - - HYPH cord-021063-4y8m33ea 94 3 I -PRON- PRP cord-021063-4y8m33ea 94 4 deletion deletion NN cord-021063-4y8m33ea 94 5 mutants mutant NNS cord-021063-4y8m33ea 94 6 have have VBP cord-021063-4y8m33ea 94 7 been be VBN cord-021063-4y8m33ea 94 8 isolated isolate VBN cord-021063-4y8m33ea 94 9 that that WDT cord-021063-4y8m33ea 94 10 are be VBP cord-021063-4y8m33ea 94 11 incapable incapable JJ cord-021063-4y8m33ea 94 12 of of IN cord-021063-4y8m33ea 94 13 reactivation reactivation NN cord-021063-4y8m33ea 94 14 , , , cord-021063-4y8m33ea 94 15 and and CC cord-021063-4y8m33ea 94 16 that that IN cord-021063-4y8m33ea 94 17 once once RB cord-021063-4y8m33ea 94 18 inserted insert VBD cord-021063-4y8m33ea 94 19 into into IN cord-021063-4y8m33ea 94 20 a a DT cord-021063-4y8m33ea 94 21 neuron neuron NN cord-021063-4y8m33ea 94 22 will will MD cord-021063-4y8m33ea 94 23 remain remain VB cord-021063-4y8m33ea 94 24 latent latent JJ cord-021063-4y8m33ea 94 25 indefinitely indefinitely RB cord-021063-4y8m33ea 94 26 . . . cord-021063-4y8m33ea 95 1 If if IN cord-021063-4y8m33ea 95 2 therapeutic therapeutic JJ cord-021063-4y8m33ea 95 3 genes gene NNS cord-021063-4y8m33ea 95 4 added add VBD cord-021063-4y8m33ea 95 5 to to IN cord-021063-4y8m33ea 95 6 these these DT cord-021063-4y8m33ea 95 7 vectors vector NNS cord-021063-4y8m33ea 95 8 have have VBP cord-021063-4y8m33ea 95 9 LAT lat NN cord-021063-4y8m33ea 95 10 promoter promoter NN cord-021063-4y8m33ea 95 11 elements element NNS cord-021063-4y8m33ea 95 12 , , , cord-021063-4y8m33ea 95 13 they -PRON- PRP cord-021063-4y8m33ea 95 14 will will MD cord-021063-4y8m33ea 95 15 be be VB cord-021063-4y8m33ea 95 16 expressed express VBN cord-021063-4y8m33ea 95 17 even even RB cord-021063-4y8m33ea 95 18 though though IN cord-021063-4y8m33ea 95 19 the the DT cord-021063-4y8m33ea 95 20 virus virus NN cord-021063-4y8m33ea 95 21 itself -PRON- PRP cord-021063-4y8m33ea 95 22 remains remain VBZ cord-021063-4y8m33ea 95 23 latent latent JJ cord-021063-4y8m33ea 95 24 . . . cord-021063-4y8m33ea 96 1 These these DT cord-021063-4y8m33ea 96 2 vectors vector NNS cord-021063-4y8m33ea 96 3 are be VBP cord-021063-4y8m33ea 96 4 being be VBG cord-021063-4y8m33ea 96 5 developed develop VBN cord-021063-4y8m33ea 96 6 for for IN cord-021063-4y8m33ea 96 7 the the DT cord-021063-4y8m33ea 96 8 introduction introduction NN cord-021063-4y8m33ea 96 9 of of IN cord-021063-4y8m33ea 96 10 genes gene NNS cord-021063-4y8m33ea 96 11 into into IN cord-021063-4y8m33ea 96 12 cells cell NNS cord-021063-4y8m33ea 96 13 of of IN cord-021063-4y8m33ea 96 14 the the DT cord-021063-4y8m33ea 96 15 central central JJ cord-021063-4y8m33ea 96 16 nervous nervous JJ cord-021063-4y8m33ea 96 17 system system NN cord-021063-4y8m33ea 96 18 ( ( -LRB- cord-021063-4y8m33ea 96 19 Geller Geller NNP cord-021063-4y8m33ea 96 20 , , , cord-021063-4y8m33ea 96 21 1993 1993 CD cord-021063-4y8m33ea 96 22 ) ) -RRB- cord-021063-4y8m33ea 96 23 . . . cord-021063-4y8m33ea 97 1 In in IN cord-021063-4y8m33ea 97 2 summary summary NN cord-021063-4y8m33ea 97 3 , , , cord-021063-4y8m33ea 97 4 all all DT cord-021063-4y8m33ea 97 5 viral viral JJ cord-021063-4y8m33ea 97 6 methods method NNS cord-021063-4y8m33ea 97 7 of of IN cord-021063-4y8m33ea 97 8 gene gene NN cord-021063-4y8m33ea 97 9 therapy therapy NN cord-021063-4y8m33ea 97 10 share share NN cord-021063-4y8m33ea 97 11 several several JJ cord-021063-4y8m33ea 97 12 strengths strength NNS cord-021063-4y8m33ea 97 13 , , , cord-021063-4y8m33ea 97 14 as as RB cord-021063-4y8m33ea 97 15 well well RB cord-021063-4y8m33ea 97 16 as as IN cord-021063-4y8m33ea 97 17 numerous numerous JJ cord-021063-4y8m33ea 97 18 weaknesses weakness NNS cord-021063-4y8m33ea 97 19 . . . cord-021063-4y8m33ea 98 1 It -PRON- PRP cord-021063-4y8m33ea 98 2 is be VBZ cord-021063-4y8m33ea 98 3 relatively relatively RB cord-021063-4y8m33ea 98 4 easy easy JJ cord-021063-4y8m33ea 98 5 to to TO cord-021063-4y8m33ea 98 6 produce produce VB cord-021063-4y8m33ea 98 7 the the DT cord-021063-4y8m33ea 98 8 large large JJ cord-021063-4y8m33ea 98 9 amounts amount NNS cord-021063-4y8m33ea 98 10 of of IN cord-021063-4y8m33ea 98 11 virus virus NN cord-021063-4y8m33ea 98 12 necessary necessary JJ cord-021063-4y8m33ea 98 13 to to TO cord-021063-4y8m33ea 98 14 treat treat VB cord-021063-4y8m33ea 98 15 patients patient NNS cord-021063-4y8m33ea 98 16 . . . cord-021063-4y8m33ea 99 1 Viruses virus NNS cord-021063-4y8m33ea 99 2 efficiently efficiently RB cord-021063-4y8m33ea 99 3 infect infect VBP cord-021063-4y8m33ea 99 4 a a DT cord-021063-4y8m33ea 99 5 large large JJ cord-021063-4y8m33ea 99 6 fraction fraction NN cord-021063-4y8m33ea 99 7 of of IN cord-021063-4y8m33ea 99 8 the the DT cord-021063-4y8m33ea 99 9 cells cell NNS cord-021063-4y8m33ea 99 10 with with IN cord-021063-4y8m33ea 99 11 which which WDT cord-021063-4y8m33ea 99 12 they -PRON- PRP cord-021063-4y8m33ea 99 13 come come VBP cord-021063-4y8m33ea 99 14 in in IN cord-021063-4y8m33ea 99 15 contact contact NN cord-021063-4y8m33ea 99 16 . . . cord-021063-4y8m33ea 100 1 Although although IN cord-021063-4y8m33ea 100 2 this this DT cord-021063-4y8m33ea 100 3 may may MD cord-021063-4y8m33ea 100 4 be be VB cord-021063-4y8m33ea 100 5 a a DT cord-021063-4y8m33ea 100 6 drawback drawback NN cord-021063-4y8m33ea 100 7 in in IN cord-021063-4y8m33ea 100 8 some some DT cord-021063-4y8m33ea 100 9 cases case NNS cord-021063-4y8m33ea 100 10 where where WRB cord-021063-4y8m33ea 100 11 expression expression NN cord-021063-4y8m33ea 100 12 of of IN cord-021063-4y8m33ea 100 13 the the DT cord-021063-4y8m33ea 100 14 therapeutic therapeutic JJ cord-021063-4y8m33ea 100 15 gene gene NN cord-021063-4y8m33ea 100 16 must must MD cord-021063-4y8m33ea 100 17 be be VB cord-021063-4y8m33ea 100 18 restricted restrict VBN cord-021063-4y8m33ea 100 19 to to IN cord-021063-4y8m33ea 100 20 specific specific JJ cord-021063-4y8m33ea 100 21 cells cell NNS cord-021063-4y8m33ea 100 22 , , , cord-021063-4y8m33ea 100 23 it -PRON- PRP cord-021063-4y8m33ea 100 24 may may MD cord-021063-4y8m33ea 100 25 be be VB cord-021063-4y8m33ea 100 26 possible possible JJ cord-021063-4y8m33ea 100 27 to to TO cord-021063-4y8m33ea 100 28 limit limit VB cord-021063-4y8m33ea 100 29 unwanted unwanted JJ cord-021063-4y8m33ea 100 30 expression expression NN cord-021063-4y8m33ea 100 31 of of IN cord-021063-4y8m33ea 100 32 the the DT cord-021063-4y8m33ea 100 33 inserted insert VBN cord-021063-4y8m33ea 100 34 gene gene NN cord-021063-4y8m33ea 100 35 by by IN cord-021063-4y8m33ea 100 36 the the DT cord-021063-4y8m33ea 100 37 use use NN cord-021063-4y8m33ea 100 38 of of IN cord-021063-4y8m33ea 100 39 tissue tissue NN cord-021063-4y8m33ea 100 40 - - HYPH cord-021063-4y8m33ea 100 41 specific specific JJ cord-021063-4y8m33ea 100 42 promoters promoter NNS cord-021063-4y8m33ea 100 43 . . . cord-021063-4y8m33ea 101 1 All all DT cord-021063-4y8m33ea 101 2 viral viral JJ cord-021063-4y8m33ea 101 3 vectors vector NNS cord-021063-4y8m33ea 101 4 for for IN cord-021063-4y8m33ea 101 5 human human JJ cord-021063-4y8m33ea 101 6 gene gene NN cord-021063-4y8m33ea 101 7 therapy therapy NN cord-021063-4y8m33ea 101 8 are be VBP cord-021063-4y8m33ea 101 9 derived derive VBN cord-021063-4y8m33ea 101 10 from from IN cord-021063-4y8m33ea 101 11 organisms organism NNS cord-021063-4y8m33ea 101 12 that that WDT cord-021063-4y8m33ea 101 13 cause cause VBP cord-021063-4y8m33ea 101 14 human human JJ cord-021063-4y8m33ea 101 15 disease disease NN cord-021063-4y8m33ea 101 16 . . . cord-021063-4y8m33ea 102 1 The the DT cord-021063-4y8m33ea 102 2 possibility possibility NN cord-021063-4y8m33ea 102 3 of of IN cord-021063-4y8m33ea 102 4 reactivation reactivation NN cord-021063-4y8m33ea 102 5 of of IN cord-021063-4y8m33ea 102 6 the the DT cord-021063-4y8m33ea 102 7 vectors vector NNS cord-021063-4y8m33ea 102 8 ' ' POS cord-021063-4y8m33ea 102 9 infectivity infectivity NN cord-021063-4y8m33ea 102 10 or or CC cord-021063-4y8m33ea 102 11 pathogenicity pathogenicity NN cord-021063-4y8m33ea 102 12 is be VBZ cord-021063-4y8m33ea 102 13 hard hard JJ cord-021063-4y8m33ea 102 14 to to TO cord-021063-4y8m33ea 102 15 dismiss dismiss VB cord-021063-4y8m33ea 102 16 . . . cord-021063-4y8m33ea 103 1 In in IN cord-021063-4y8m33ea 103 2 the the DT cord-021063-4y8m33ea 103 3 end end NN cord-021063-4y8m33ea 103 4 , , , cord-021063-4y8m33ea 103 5 it -PRON- PRP cord-021063-4y8m33ea 103 6 may may MD cord-021063-4y8m33ea 103 7 prove prove VB cord-021063-4y8m33ea 103 8 easier easy JJR cord-021063-4y8m33ea 103 9 and and CC cord-021063-4y8m33ea 103 10 safer safe JJR cord-021063-4y8m33ea 103 11 to to TO cord-021063-4y8m33ea 103 12 construct construct VB cord-021063-4y8m33ea 103 13 a a DT cord-021063-4y8m33ea 103 14 gene gene NN cord-021063-4y8m33ea 103 15 therapy therapy NN cord-021063-4y8m33ea 103 16 vector vector NN cord-021063-4y8m33ea 103 17 having have VBG cord-021063-4y8m33ea 103 18 the the DT cord-021063-4y8m33ea 103 19 elements element NNS cord-021063-4y8m33ea 103 20 of of IN cord-021063-4y8m33ea 103 21 a a DT cord-021063-4y8m33ea 103 22 successful successful JJ cord-021063-4y8m33ea 103 23 virus virus NN cord-021063-4y8m33ea 103 24 , , , cord-021063-4y8m33ea 103 25 but but CC cord-021063-4y8m33ea 103 26 derived derive VBN cord-021063-4y8m33ea 103 27 from from IN cord-021063-4y8m33ea 103 28 completely completely RB cord-021063-4y8m33ea 103 29 synthetic synthetic JJ cord-021063-4y8m33ea 103 30 components component NNS cord-021063-4y8m33ea 103 31 . . . cord-021063-4y8m33ea 104 1 One one CD cord-021063-4y8m33ea 104 2 such such JJ cord-021063-4y8m33ea 104 3 strategy strategy NN cord-021063-4y8m33ea 104 4 involves involve VBZ cord-021063-4y8m33ea 104 5 the the DT cord-021063-4y8m33ea 104 6 use use NN cord-021063-4y8m33ea 104 7 of of IN cord-021063-4y8m33ea 104 8 liposomes liposome NNS cord-021063-4y8m33ea 104 9 . . . cord-021063-4y8m33ea 105 1 Liposomes liposome NNS cord-021063-4y8m33ea 105 2 are be VBP cord-021063-4y8m33ea 105 3 small small JJ cord-021063-4y8m33ea 105 4 vesicles vesicle NNS cord-021063-4y8m33ea 105 5 usually usually RB cord-021063-4y8m33ea 105 6 made make VBN cord-021063-4y8m33ea 105 7 from from IN cord-021063-4y8m33ea 105 8 pure pure JJ cord-021063-4y8m33ea 105 9 preparations preparation NNS cord-021063-4y8m33ea 105 10 of of IN cord-021063-4y8m33ea 105 11 phospholipids phospholipid NNS cord-021063-4y8m33ea 105 12 . . . cord-021063-4y8m33ea 106 1 Because because IN cord-021063-4y8m33ea 106 2 they -PRON- PRP cord-021063-4y8m33ea 106 3 can can MD cord-021063-4y8m33ea 106 4 be be VB cord-021063-4y8m33ea 106 5 made make VBN cord-021063-4y8m33ea 106 6 from from IN cord-021063-4y8m33ea 106 7 completely completely RB cord-021063-4y8m33ea 106 8 pure pure JJ cord-021063-4y8m33ea 106 9 components component NNS cord-021063-4y8m33ea 106 10 , , , cord-021063-4y8m33ea 106 11 they -PRON- PRP cord-021063-4y8m33ea 106 12 have have VBP cord-021063-4y8m33ea 106 13 been be VBN cord-021063-4y8m33ea 106 14 used use VBN cord-021063-4y8m33ea 106 15 extensively extensively RB cord-021063-4y8m33ea 106 16 to to TO cord-021063-4y8m33ea 106 17 characterize characterize VB cord-021063-4y8m33ea 106 18 and and CC cord-021063-4y8m33ea 106 19 define define VB cord-021063-4y8m33ea 106 20 the the DT cord-021063-4y8m33ea 106 21 physical physical JJ cord-021063-4y8m33ea 106 22 properties property NNS cord-021063-4y8m33ea 106 23 of of IN cord-021063-4y8m33ea 106 24 membranes membrane NNS cord-021063-4y8m33ea 106 25 and and CC cord-021063-4y8m33ea 106 26 membrane membrane NN cord-021063-4y8m33ea 106 27 proteins protein NNS cord-021063-4y8m33ea 106 28 . . . cord-021063-4y8m33ea 107 1 Liposomes liposome NNS cord-021063-4y8m33ea 107 2 have have VBP cord-021063-4y8m33ea 107 3 also also RB cord-021063-4y8m33ea 107 4 been be VBN cord-021063-4y8m33ea 107 5 used use VBN cord-021063-4y8m33ea 107 6 as as IN cord-021063-4y8m33ea 107 7 a a DT cord-021063-4y8m33ea 107 8 means means NN cord-021063-4y8m33ea 107 9 of of IN cord-021063-4y8m33ea 107 10 delivering deliver VBG cord-021063-4y8m33ea 107 11 substances substance NNS cord-021063-4y8m33ea 107 12 to to IN cord-021063-4y8m33ea 107 13 cells cell NNS cord-021063-4y8m33ea 107 14 , , , cord-021063-4y8m33ea 107 15 both both CC cord-021063-4y8m33ea 107 16 in in IN cord-021063-4y8m33ea 107 17 vitro vitro FW cord-021063-4y8m33ea 107 18 and and CC cord-021063-4y8m33ea 107 19 in in IN cord-021063-4y8m33ea 107 20 vivo vivo NN cord-021063-4y8m33ea 107 21 , , , cord-021063-4y8m33ea 107 22 including include VBG cord-021063-4y8m33ea 107 23 DNA dna NN cord-021063-4y8m33ea 107 24 ( ( -LRB- cord-021063-4y8m33ea 107 25 Hug Hug NNP cord-021063-4y8m33ea 107 26 and and CC cord-021063-4y8m33ea 107 27 Sleight Sleight NNP cord-021063-4y8m33ea 107 28 , , , cord-021063-4y8m33ea 107 29 1991 1991 CD cord-021063-4y8m33ea 107 30 ) ) -RRB- cord-021063-4y8m33ea 107 31 . . . cord-021063-4y8m33ea 108 1 Before before IN cord-021063-4y8m33ea 108 2 discussing discuss VBG cord-021063-4y8m33ea 108 3 factors factor NNS cord-021063-4y8m33ea 108 4 to to TO cord-021063-4y8m33ea 108 5 be be VB cord-021063-4y8m33ea 108 6 considered consider VBN cord-021063-4y8m33ea 108 7 in in IN cord-021063-4y8m33ea 108 8 preparing prepare VBG cord-021063-4y8m33ea 108 9 liposomes liposome NNS cord-021063-4y8m33ea 108 10 for for IN cord-021063-4y8m33ea 108 11 gene gene NN cord-021063-4y8m33ea 108 12 therapy therapy NN cord-021063-4y8m33ea 108 13 of of IN cord-021063-4y8m33ea 108 14 a a DT cord-021063-4y8m33ea 108 15 given give VBN cord-021063-4y8m33ea 108 16 disease disease NN cord-021063-4y8m33ea 108 17 , , , cord-021063-4y8m33ea 108 18 it -PRON- PRP cord-021063-4y8m33ea 108 19 is be VBZ cord-021063-4y8m33ea 108 20 worthwhile worthwhile JJ cord-021063-4y8m33ea 108 21 to to TO cord-021063-4y8m33ea 108 22 review review VB cord-021063-4y8m33ea 108 23 some some DT cord-021063-4y8m33ea 108 24 general general JJ cord-021063-4y8m33ea 108 25 aspects aspect NNS cord-021063-4y8m33ea 108 26 of of IN cord-021063-4y8m33ea 108 27 liposome liposome NN cord-021063-4y8m33ea 108 28 preparation preparation NN cord-021063-4y8m33ea 108 29 and and CC cord-021063-4y8m33ea 108 30 design design NN cord-021063-4y8m33ea 108 31 . . . cord-021063-4y8m33ea 109 1 Liposomes liposome NNS cord-021063-4y8m33ea 109 2 are be VBP cord-021063-4y8m33ea 109 3 generally generally RB cord-021063-4y8m33ea 109 4 classified classify VBN cord-021063-4y8m33ea 109 5 by by IN cord-021063-4y8m33ea 109 6 the the DT cord-021063-4y8m33ea 109 7 number number NN cord-021063-4y8m33ea 109 8 of of IN cord-021063-4y8m33ea 109 9 bilayers bilayer NNS cord-021063-4y8m33ea 109 10 ( ( -LRB- cord-021063-4y8m33ea 109 11 lamellae lamella NNS cord-021063-4y8m33ea 109 12 ) ) -RRB- cord-021063-4y8m33ea 109 13 they -PRON- PRP cord-021063-4y8m33ea 109 14 contain contain VBP cord-021063-4y8m33ea 109 15 , , , cord-021063-4y8m33ea 109 16 by by IN cord-021063-4y8m33ea 109 17 size size NN cord-021063-4y8m33ea 109 18 , , , cord-021063-4y8m33ea 109 19 and and CC cord-021063-4y8m33ea 109 20 by by IN cord-021063-4y8m33ea 109 21 the the DT cord-021063-4y8m33ea 109 22 composition composition NN cord-021063-4y8m33ea 109 23 of of IN cord-021063-4y8m33ea 109 24 their -PRON- PRP$ cord-021063-4y8m33ea 109 25 membrane membrane NN cord-021063-4y8m33ea 109 26 . . . cord-021063-4y8m33ea 110 1 The the DT cord-021063-4y8m33ea 110 2 earliest early JJS cord-021063-4y8m33ea 110 3 liposomes liposome NNS cord-021063-4y8m33ea 110 4 were be VBD cord-021063-4y8m33ea 110 5 formed form VBN cord-021063-4y8m33ea 110 6 by by IN cord-021063-4y8m33ea 110 7 hydration hydration NN cord-021063-4y8m33ea 110 8 of of IN cord-021063-4y8m33ea 110 9 a a DT cord-021063-4y8m33ea 110 10 dried dry VBN cord-021063-4y8m33ea 110 11 lipid lipid NN cord-021063-4y8m33ea 110 12 film film NN cord-021063-4y8m33ea 110 13 , , , cord-021063-4y8m33ea 110 14 followed follow VBN cord-021063-4y8m33ea 110 15 by by IN cord-021063-4y8m33ea 110 16 vortexing vortexe VBG cord-021063-4y8m33ea 110 17 . . . cord-021063-4y8m33ea 111 1 This this DT cord-021063-4y8m33ea 111 2 results result VBZ cord-021063-4y8m33ea 111 3 in in IN cord-021063-4y8m33ea 111 4 a a DT cord-021063-4y8m33ea 111 5 cloudy cloudy JJ cord-021063-4y8m33ea 111 6 solution solution NN cord-021063-4y8m33ea 111 7 of of IN cord-021063-4y8m33ea 111 8 liposomes liposome NNS cord-021063-4y8m33ea 111 9 having have VBG cord-021063-4y8m33ea 111 10 many many JJ cord-021063-4y8m33ea 111 11 lamellar lamellar JJ cord-021063-4y8m33ea 111 12 layers layer NNS cord-021063-4y8m33ea 111 13 , , , cord-021063-4y8m33ea 111 14 resembling resemble VBG cord-021063-4y8m33ea 111 15 an an DT cord-021063-4y8m33ea 111 16 onion onion NN cord-021063-4y8m33ea 111 17 . . . cord-021063-4y8m33ea 112 1 These these DT cord-021063-4y8m33ea 112 2 are be VBP cord-021063-4y8m33ea 112 3 called call VBN cord-021063-4y8m33ea 112 4 multilamellar multilamellar JJ cord-021063-4y8m33ea 112 5 vesicles vesicle NNS cord-021063-4y8m33ea 112 6 , , , cord-021063-4y8m33ea 112 7 or or CC cord-021063-4y8m33ea 112 8 MLVs mlv NNS cord-021063-4y8m33ea 112 9 . . . cord-021063-4y8m33ea 113 1 Although although IN cord-021063-4y8m33ea 113 2 MLVs mlv NNS cord-021063-4y8m33ea 113 3 are be VBP cord-021063-4y8m33ea 113 4 effective effective JJ cord-021063-4y8m33ea 113 5 for for IN cord-021063-4y8m33ea 113 6 the the DT cord-021063-4y8m33ea 113 7 packaging packaging NN cord-021063-4y8m33ea 113 8 of of IN cord-021063-4y8m33ea 113 9 lipophilic lipophilic JJ cord-021063-4y8m33ea 113 10 drugs drug NNS cord-021063-4y8m33ea 113 11 , , , cord-021063-4y8m33ea 113 12 they -PRON- PRP cord-021063-4y8m33ea 113 13 have have VBP cord-021063-4y8m33ea 113 14 very very RB cord-021063-4y8m33ea 113 15 little little JJ cord-021063-4y8m33ea 113 16 aqueous aqueous JJ cord-021063-4y8m33ea 113 17 volume volume NN cord-021063-4y8m33ea 113 18 in in IN cord-021063-4y8m33ea 113 19 their -PRON- PRP$ cord-021063-4y8m33ea 113 20 interiors interior NNS cord-021063-4y8m33ea 113 21 , , , cord-021063-4y8m33ea 113 22 and and CC cord-021063-4y8m33ea 113 23 are be VBP cord-021063-4y8m33ea 113 24 not not RB cord-021063-4y8m33ea 113 25 efficient efficient JJ cord-021063-4y8m33ea 113 26 at at IN cord-021063-4y8m33ea 113 27 entrapping entrap VBG cord-021063-4y8m33ea 113 28 water water NN cord-021063-4y8m33ea 113 29 - - HYPH cord-021063-4y8m33ea 113 30 soluble soluble JJ cord-021063-4y8m33ea 113 31 compounds compound NNS cord-021063-4y8m33ea 113 32 or or CC cord-021063-4y8m33ea 113 33 large large JJ cord-021063-4y8m33ea 113 34 DNA dna NN cord-021063-4y8m33ea 113 35 fragments fragment NNS cord-021063-4y8m33ea 113 36 . . . cord-021063-4y8m33ea 114 1 Because because IN cord-021063-4y8m33ea 114 2 of of IN cord-021063-4y8m33ea 114 3 these these DT cord-021063-4y8m33ea 114 4 deficiencies deficiency NNS cord-021063-4y8m33ea 114 5 , , , cord-021063-4y8m33ea 114 6 MLVs mlv NNS cord-021063-4y8m33ea 114 7 were be VBD cord-021063-4y8m33ea 114 8 quickly quickly RB cord-021063-4y8m33ea 114 9 superseded supersede VBN cord-021063-4y8m33ea 114 10 by by IN cord-021063-4y8m33ea 114 11 unilamellar unilamellar NNP cord-021063-4y8m33ea 114 12 vesicles vesicle NNS cord-021063-4y8m33ea 114 13 , , , cord-021063-4y8m33ea 114 14 which which WDT cord-021063-4y8m33ea 114 15 have have VBP cord-021063-4y8m33ea 114 16 only only RB cord-021063-4y8m33ea 114 17 a a DT cord-021063-4y8m33ea 114 18 single single JJ cord-021063-4y8m33ea 114 19 lipid lipid NN cord-021063-4y8m33ea 114 20 bilayer bilayer NN cord-021063-4y8m33ea 114 21 between between IN cord-021063-4y8m33ea 114 22 the the DT cord-021063-4y8m33ea 114 23 external external JJ cord-021063-4y8m33ea 114 24 fluid fluid NN cord-021063-4y8m33ea 114 25 and and CC cord-021063-4y8m33ea 114 26 the the DT cord-021063-4y8m33ea 114 27 lumen lumen NN cord-021063-4y8m33ea 114 28 . . . cord-021063-4y8m33ea 115 1 Several several JJ cord-021063-4y8m33ea 115 2 methods method NNS cord-021063-4y8m33ea 115 3 are be VBP cord-021063-4y8m33ea 115 4 used use VBN cord-021063-4y8m33ea 115 5 to to TO cord-021063-4y8m33ea 115 6 pre pre VB cord-021063-4y8m33ea 115 7 ~ ~ NNP cord-021063-4y8m33ea 115 8 pare pare VB cord-021063-4y8m33ea 115 9 unilamellar unilamellar NNP cord-021063-4y8m33ea 115 10 vesicles vesicle NNS cord-021063-4y8m33ea 115 11 , , , cord-021063-4y8m33ea 115 12 each each DT cord-021063-4y8m33ea 115 13 having have VBG cord-021063-4y8m33ea 115 14 its -PRON- PRP$ cord-021063-4y8m33ea 115 15 own own JJ cord-021063-4y8m33ea 115 16 advantages advantage NNS cord-021063-4y8m33ea 115 17 and and CC cord-021063-4y8m33ea 115 18 disadvantages disadvantage NNS cord-021063-4y8m33ea 115 19 . . . cord-021063-4y8m33ea 116 1 Because because IN cord-021063-4y8m33ea 116 2 of of IN cord-021063-4y8m33ea 116 3 space space NN cord-021063-4y8m33ea 116 4 limitations limitation NNS cord-021063-4y8m33ea 116 5 , , , cord-021063-4y8m33ea 116 6 we -PRON- PRP cord-021063-4y8m33ea 116 7 will will MD cord-021063-4y8m33ea 116 8 only only RB cord-021063-4y8m33ea 116 9 briefly briefly RB cord-021063-4y8m33ea 116 10 describe describe VB cord-021063-4y8m33ea 116 11 those those DT cord-021063-4y8m33ea 116 12 methods method NNS cord-021063-4y8m33ea 116 13 of of IN cord-021063-4y8m33ea 116 14 liposome liposome NN cord-021063-4y8m33ea 116 15 preparation preparation NN cord-021063-4y8m33ea 116 16 that that WDT cord-021063-4y8m33ea 116 17 are be VBP cord-021063-4y8m33ea 116 18 directly directly RB cord-021063-4y8m33ea 116 19 relevant relevant JJ cord-021063-4y8m33ea 116 20 to to IN cord-021063-4y8m33ea 116 21 the the DT cord-021063-4y8m33ea 116 22 construction construction NN cord-021063-4y8m33ea 116 23 of of IN cord-021063-4y8m33ea 116 24 gene gene NN cord-021063-4y8m33ea 116 25 therapy therapy NN cord-021063-4y8m33ea 116 26 vectors vector NNS cord-021063-4y8m33ea 116 27 . . . cord-021063-4y8m33ea 117 1 Table table NN cord-021063-4y8m33ea 117 2 3 3 CD cord-021063-4y8m33ea 117 3 gives give VBZ cord-021063-4y8m33ea 117 4 a a DT cord-021063-4y8m33ea 117 5 direct direct JJ cord-021063-4y8m33ea 117 6 comparison comparison NN cord-021063-4y8m33ea 117 7 of of IN cord-021063-4y8m33ea 117 8 these these DT cord-021063-4y8m33ea 117 9 methods method NNS cord-021063-4y8m33ea 117 10 of of IN cord-021063-4y8m33ea 117 11 preparation preparation NN cord-021063-4y8m33ea 117 12 as as IN cord-021063-4y8m33ea 117 13 related relate VBN cord-021063-4y8m33ea 117 14 to to IN cord-021063-4y8m33ea 117 15 transfection transfection NN cord-021063-4y8m33ea 117 16 . . . cord-021063-4y8m33ea 118 1 Cationic Cationic NNP cord-021063-4y8m33ea 118 2 Liposomes liposome NNS cord-021063-4y8m33ea 118 3 . . . cord-021063-4y8m33ea 119 1 Liposomes liposome NNS cord-021063-4y8m33ea 119 2 made make VBD cord-021063-4y8m33ea 119 3 entirely entirely RB cord-021063-4y8m33ea 119 4 or or CC cord-021063-4y8m33ea 119 5 partially partially RB cord-021063-4y8m33ea 119 6 of of IN cord-021063-4y8m33ea 119 7 a a DT cord-021063-4y8m33ea 119 8 cationic cationic JJ cord-021063-4y8m33ea 119 9 lipid lipid NN cord-021063-4y8m33ea 119 10 have have VBP cord-021063-4y8m33ea 119 11 a a DT cord-021063-4y8m33ea 119 12 charge charge NN cord-021063-4y8m33ea 119 13 - - HYPH cord-021063-4y8m33ea 119 14 based base VBN cord-021063-4y8m33ea 119 15 affinity affinity NN cord-021063-4y8m33ea 119 16 for for IN cord-021063-4y8m33ea 119 17 DNA dna NN cord-021063-4y8m33ea 119 18 . . . cord-021063-4y8m33ea 120 1 When when WRB cord-021063-4y8m33ea 120 2 such such JJ cord-021063-4y8m33ea 120 3 liposomes liposome NNS cord-021063-4y8m33ea 120 4 are be VBP cord-021063-4y8m33ea 120 5 incubated incubate VBN cord-021063-4y8m33ea 120 6 in in IN cord-021063-4y8m33ea 120 7 solution solution NN cord-021063-4y8m33ea 120 8 with with IN cord-021063-4y8m33ea 120 9 DNA DNA NNP cord-021063-4y8m33ea 120 10 , , , cord-021063-4y8m33ea 120 11 they -PRON- PRP cord-021063-4y8m33ea 120 12 form form VBP cord-021063-4y8m33ea 120 13 complexes complex NNS cord-021063-4y8m33ea 120 14 that that WDT cord-021063-4y8m33ea 120 15 can can MD cord-021063-4y8m33ea 120 16 transfect transfect VB cord-021063-4y8m33ea 120 17 cells cell NNS cord-021063-4y8m33ea 120 18 . . . cord-021063-4y8m33ea 121 1 Several several JJ cord-021063-4y8m33ea 121 2 types type NNS cord-021063-4y8m33ea 121 3 of of IN cord-021063-4y8m33ea 121 4 cationic cationic JJ cord-021063-4y8m33ea 121 5 lipid lipid NN cord-021063-4y8m33ea 121 6 are be VBP cord-021063-4y8m33ea 121 7 available available JJ cord-021063-4y8m33ea 121 8 which which WDT cord-021063-4y8m33ea 121 9 in in IN cord-021063-4y8m33ea 121 10 general general JJ cord-021063-4y8m33ea 121 11 have have VBP cord-021063-4y8m33ea 121 12 similar similar JJ cord-021063-4y8m33ea 121 13 characteristics characteristic NNS cord-021063-4y8m33ea 121 14 ( ( -LRB- cord-021063-4y8m33ea 121 15 Leventis Leventis NNP cord-021063-4y8m33ea 121 16 and and CC cord-021063-4y8m33ea 121 17 Silvius Silvius NNP cord-021063-4y8m33ea 121 18 , , , cord-021063-4y8m33ea 121 19 1990 1990 CD cord-021063-4y8m33ea 121 20 ; ; : cord-021063-4y8m33ea 121 21 Ito Ito NNP cord-021063-4y8m33ea 121 22 et et NNP cord-021063-4y8m33ea 121 23 al al NNP cord-021063-4y8m33ea 121 24 . . NNP cord-021063-4y8m33ea 121 25 , , , cord-021063-4y8m33ea 121 26 1990 1990 CD cord-021063-4y8m33ea 121 27 ; ; : cord-021063-4y8m33ea 121 28 Gao Gao NNP cord-021063-4y8m33ea 121 29 and and CC cord-021063-4y8m33ea 121 30 Huang Huang NNP cord-021063-4y8m33ea 121 31 , , , cord-021063-4y8m33ea 121 32 1991 1991 CD cord-021063-4y8m33ea 121 33 ; ; : cord-021063-4y8m33ea 121 34 Hazinski Hazinski NNP cord-021063-4y8m33ea 121 35 et et NNP cord-021063-4y8m33ea 121 36 al al NNP cord-021063-4y8m33ea 121 37 . . NNP cord-021063-4y8m33ea 121 38 , , , cord-021063-4y8m33ea 121 39 1991 1991 CD cord-021063-4y8m33ea 121 40 ; ; : cord-021063-4y8m33ea 121 41 Farhood Farhood NNP cord-021063-4y8m33ea 121 42 et et NNP cord-021063-4y8m33ea 121 43 al al NNP cord-021063-4y8m33ea 121 44 . . NNP cord-021063-4y8m33ea 121 45 , , , cord-021063-4y8m33ea 121 46 1992 1992 CD cord-021063-4y8m33ea 121 47 ) ) -RRB- cord-021063-4y8m33ea 121 48 . . . cord-021063-4y8m33ea 122 1 This this DT cord-021063-4y8m33ea 122 2 technique technique NN cord-021063-4y8m33ea 122 3 was be VBD cord-021063-4y8m33ea 122 4 initially initially RB cord-021063-4y8m33ea 122 5 intended intend VBN cord-021063-4y8m33ea 122 6 exclusively exclusively RB cord-021063-4y8m33ea 122 7 for for IN cord-021063-4y8m33ea 122 8 in in FW cord-021063-4y8m33ea 122 9 vitro vitro FW cord-021063-4y8m33ea 122 10 use use NN cord-021063-4y8m33ea 122 11 . . . cord-021063-4y8m33ea 123 1 However however RB cord-021063-4y8m33ea 123 2 , , , cord-021063-4y8m33ea 123 3 in in IN cord-021063-4y8m33ea 123 4 vivo vivo FW cord-021063-4y8m33ea 123 5 transfections transfection NNS cord-021063-4y8m33ea 123 6 have have VBP cord-021063-4y8m33ea 123 7 been be VBN cord-021063-4y8m33ea 123 8 performed perform VBN cord-021063-4y8m33ea 123 9 with with IN cord-021063-4y8m33ea 123 10 several several JJ cord-021063-4y8m33ea 123 11 commercial commercial JJ cord-021063-4y8m33ea 123 12 preparations preparation NNS cord-021063-4y8m33ea 123 13 of of IN cord-021063-4y8m33ea 123 14 cationic cationic JJ cord-021063-4y8m33ea 123 15 lipids lipid NNS cord-021063-4y8m33ea 123 16 . . . cord-021063-4y8m33ea 124 1 There there EX cord-021063-4y8m33ea 124 2 are be VBP cord-021063-4y8m33ea 124 3 several several JJ cord-021063-4y8m33ea 124 4 reasons reason NNS cord-021063-4y8m33ea 124 5 why why WRB cord-021063-4y8m33ea 124 6 cationic cationic JJ cord-021063-4y8m33ea 124 7 lipid lipid NN cord-021063-4y8m33ea 124 8 - - HYPH cord-021063-4y8m33ea 124 9 DNA dna NN cord-021063-4y8m33ea 124 10 complexes complex NNS cord-021063-4y8m33ea 124 11 have have VBP cord-021063-4y8m33ea 124 12 proved prove VBN cord-021063-4y8m33ea 124 13 so so RB cord-021063-4y8m33ea 124 14 popular popular JJ cord-021063-4y8m33ea 124 15 for for IN cord-021063-4y8m33ea 124 16 transfections transfection NNS cord-021063-4y8m33ea 124 17 : : : cord-021063-4y8m33ea 125 1 ( ( -LRB- cord-021063-4y8m33ea 125 2 i i NN cord-021063-4y8m33ea 125 3 ) ) -RRB- cord-021063-4y8m33ea 126 1 They -PRON- PRP cord-021063-4y8m33ea 126 2 are be VBP cord-021063-4y8m33ea 126 3 very very RB cord-021063-4y8m33ea 126 4 easy easy JJ cord-021063-4y8m33ea 126 5 to to TO cord-021063-4y8m33ea 126 6 prepare prepare VB cord-021063-4y8m33ea 126 7 . . . cord-021063-4y8m33ea 127 1 The the DT cord-021063-4y8m33ea 127 2 liposomes liposome NNS cord-021063-4y8m33ea 127 3 and and CC cord-021063-4y8m33ea 127 4 the the DT cord-021063-4y8m33ea 127 5 DNA dna NN cord-021063-4y8m33ea 127 6 are be VBP cord-021063-4y8m33ea 127 7 incubated incubate VBN cord-021063-4y8m33ea 127 8 together together RB cord-021063-4y8m33ea 127 9 , , , cord-021063-4y8m33ea 127 10 and and CC cord-021063-4y8m33ea 127 11 then then RB cord-021063-4y8m33ea 127 12 used use VBN cord-021063-4y8m33ea 127 13 without without IN cord-021063-4y8m33ea 127 14 further further JJ cord-021063-4y8m33ea 127 15 preparation preparation NN cord-021063-4y8m33ea 127 16 . . . cord-021063-4y8m33ea 128 1 ( ( -LRB- cord-021063-4y8m33ea 128 2 ii ii NN cord-021063-4y8m33ea 128 3 ) ) -RRB- cord-021063-4y8m33ea 129 1 The the DT cord-021063-4y8m33ea 129 2 complexes complex NNS cord-021063-4y8m33ea 129 3 are be VBP cord-021063-4y8m33ea 129 4 relatively relatively RB cord-021063-4y8m33ea 129 5 non non JJ cord-021063-4y8m33ea 129 6 - - JJ cord-021063-4y8m33ea 129 7 toxic toxic JJ cord-021063-4y8m33ea 129 8 . . . cord-021063-4y8m33ea 130 1 ( ( -LRB- cord-021063-4y8m33ea 130 2 iii iii NN cord-021063-4y8m33ea 130 3 ) ) -RRB- cord-021063-4y8m33ea 131 1 Transfections transfection NNS cord-021063-4y8m33ea 131 2 using use VBG cord-021063-4y8m33ea 131 3 this this DT cord-021063-4y8m33ea 131 4 method method NN cord-021063-4y8m33ea 131 5 are be VBP cord-021063-4y8m33ea 131 6 efficient efficient JJ cord-021063-4y8m33ea 131 7 with with IN cord-021063-4y8m33ea 131 8 most most JJS cord-021063-4y8m33ea 131 9 cell cell NN cord-021063-4y8m33ea 131 10 types type NNS cord-021063-4y8m33ea 131 11 . . . cord-021063-4y8m33ea 132 1 And and CC cord-021063-4y8m33ea 132 2 ( ( -LRB- cord-021063-4y8m33ea 132 3 iv iv LS cord-021063-4y8m33ea 132 4 ) ) -RRB- cord-021063-4y8m33ea 132 5 because because IN cord-021063-4y8m33ea 132 6 the the DT cord-021063-4y8m33ea 132 7 DNA dna NN cord-021063-4y8m33ea 132 8 remains remain VBZ cord-021063-4y8m33ea 132 9 outside outside IN cord-021063-4y8m33ea 132 10 the the DT cord-021063-4y8m33ea 132 11 liposome liposome NN cord-021063-4y8m33ea 132 12 , , , cord-021063-4y8m33ea 132 13 questions question NNS cord-021063-4y8m33ea 132 14 of of IN cord-021063-4y8m33ea 132 15 entrapment entrapment NN cord-021063-4y8m33ea 132 16 efficiency efficiency NN cord-021063-4y8m33ea 132 17 do do VBP cord-021063-4y8m33ea 132 18 not not RB cord-021063-4y8m33ea 132 19 apply apply VB cord-021063-4y8m33ea 132 20 . . . cord-021063-4y8m33ea 133 1 In in IN cord-021063-4y8m33ea 133 2 vivo vivo FW cord-021063-4y8m33ea 133 3 transfections transfection NNS cord-021063-4y8m33ea 133 4 using use VBG cord-021063-4y8m33ea 133 5 cationic cationic JJ cord-021063-4y8m33ea 133 6 lipid lipid NN cord-021063-4y8m33ea 133 7 - - HYPH cord-021063-4y8m33ea 133 8 DNA dna NN cord-021063-4y8m33ea 133 9 complexes complex NNS cord-021063-4y8m33ea 133 10 are be VBP cord-021063-4y8m33ea 133 11 completely completely RB cord-021063-4y8m33ea 133 12 uncontrolled uncontrolled JJ cord-021063-4y8m33ea 133 13 . . . cord-021063-4y8m33ea 134 1 That that RB cord-021063-4y8m33ea 134 2 is is RB cord-021063-4y8m33ea 134 3 , , , cord-021063-4y8m33ea 134 4 there there EX cord-021063-4y8m33ea 134 5 are be VBP cord-021063-4y8m33ea 134 6 no no DT cord-021063-4y8m33ea 134 7 targeting targeting JJ cord-021063-4y8m33ea 134 8 or or CC cord-021063-4y8m33ea 134 9 specific specific JJ cord-021063-4y8m33ea 134 10 binding bind VBG cord-021063-4y8m33ea 134 11 agents agent NNS cord-021063-4y8m33ea 134 12 present present JJ cord-021063-4y8m33ea 134 13 , , , cord-021063-4y8m33ea 134 14 and and CC cord-021063-4y8m33ea 134 15 the the DT cord-021063-4y8m33ea 134 16 complexes complex NNS cord-021063-4y8m33ea 134 17 probably probably RB cord-021063-4y8m33ea 134 18 deliver deliver VBP cord-021063-4y8m33ea 134 19 DNA DNA NNP cord-021063-4y8m33ea 134 20 to to IN cord-021063-4y8m33ea 134 21 the the DT cord-021063-4y8m33ea 134 22 first first JJ cord-021063-4y8m33ea 134 23 cell cell NN cord-021063-4y8m33ea 134 24 they -PRON- PRP cord-021063-4y8m33ea 134 25 contact contact VBP cord-021063-4y8m33ea 134 26 . . . cord-021063-4y8m33ea 135 1 This this DT cord-021063-4y8m33ea 135 2 occurs occur VBZ cord-021063-4y8m33ea 135 3 most most RBS cord-021063-4y8m33ea 135 4 often often RB cord-021063-4y8m33ea 135 5 in in IN cord-021063-4y8m33ea 135 6 the the DT cord-021063-4y8m33ea 135 7 first first JJ cord-021063-4y8m33ea 135 8 capillary capillary JJ cord-021063-4y8m33ea 135 9 bed bed NN cord-021063-4y8m33ea 135 10 through through IN cord-021063-4y8m33ea 135 11 which which WDT cord-021063-4y8m33ea 135 12 the the DT cord-021063-4y8m33ea 135 13 injected inject VBN cord-021063-4y8m33ea 135 14 complexes complex NNS cord-021063-4y8m33ea 135 15 pass pass VBP cord-021063-4y8m33ea 135 16 . . . cord-021063-4y8m33ea 136 1 When when WRB cord-021063-4y8m33ea 136 2 DNA dna NN cord-021063-4y8m33ea 136 3 - - HYPH cord-021063-4y8m33ea 136 4 lipid lipid NN cord-021063-4y8m33ea 136 5 complexes complex NNS cord-021063-4y8m33ea 136 6 are be VBP cord-021063-4y8m33ea 136 7 intravenously intravenously RB cord-021063-4y8m33ea 136 8 injected inject VBN cord-021063-4y8m33ea 136 9 , , , cord-021063-4y8m33ea 136 10 the the DT cord-021063-4y8m33ea 136 11 highest high JJS cord-021063-4y8m33ea 136 12 levels level NNS cord-021063-4y8m33ea 136 13 of of IN cord-021063-4y8m33ea 136 14 gene gene NN cord-021063-4y8m33ea 136 15 expression expression NN cord-021063-4y8m33ea 136 16 are be VBP cord-021063-4y8m33ea 136 17 usually usually RB cord-021063-4y8m33ea 136 18 seen see VBN cord-021063-4y8m33ea 136 19 in in IN cord-021063-4y8m33ea 136 20 the the DT cord-021063-4y8m33ea 136 21 pulmonary pulmonary JJ cord-021063-4y8m33ea 136 22 vascular vascular JJ cord-021063-4y8m33ea 136 23 endothelium endothelium NN cord-021063-4y8m33ea 136 24 ( ( -LRB- cord-021063-4y8m33ea 136 25 Brigham Brigham NNP cord-021063-4y8m33ea 136 26 et et NNP cord-021063-4y8m33ea 136 27 al al NNP cord-021063-4y8m33ea 136 28 . . NNP cord-021063-4y8m33ea 136 29 , , , cord-021063-4y8m33ea 136 30 1993 1993 CD cord-021063-4y8m33ea 136 31 ) ) -RRB- cord-021063-4y8m33ea 136 32 . . . cord-021063-4y8m33ea 137 1 DNA dna NN cord-021063-4y8m33ea 137 2 - - HYPH cord-021063-4y8m33ea 137 3 lipid lipid NN cord-021063-4y8m33ea 137 4 complexes complex NNS cord-021063-4y8m33ea 137 5 introduced introduce VBN cord-021063-4y8m33ea 137 6 into into IN cord-021063-4y8m33ea 137 7 the the DT cord-021063-4y8m33ea 137 8 airway airway NN cord-021063-4y8m33ea 137 9 cause cause NN cord-021063-4y8m33ea 137 10 a a DT cord-021063-4y8m33ea 137 11 generalized generalized JJ cord-021063-4y8m33ea 137 12 transfection transfection NN cord-021063-4y8m33ea 137 13 of of IN cord-021063-4y8m33ea 137 14 the the DT cord-021063-4y8m33ea 137 15 lung lung NN cord-021063-4y8m33ea 137 16 . . . cord-021063-4y8m33ea 138 1 Because because IN cord-021063-4y8m33ea 138 2 the the DT cord-021063-4y8m33ea 138 3 site site NN cord-021063-4y8m33ea 138 4 of of IN cord-021063-4y8m33ea 138 5 transfection transfection NN cord-021063-4y8m33ea 138 6 is be VBZ cord-021063-4y8m33ea 138 7 completely completely RB cord-021063-4y8m33ea 138 8 uncontrolled uncontrolled JJ cord-021063-4y8m33ea 138 9 , , , cord-021063-4y8m33ea 138 10 expression expression NN cord-021063-4y8m33ea 138 11 of of IN cord-021063-4y8m33ea 138 12 the the DT cord-021063-4y8m33ea 138 13 inserted insert VBN cord-021063-4y8m33ea 138 14 gene gene NN cord-021063-4y8m33ea 138 15 may may MD cord-021063-4y8m33ea 138 16 need need VB cord-021063-4y8m33ea 138 17 to to TO cord-021063-4y8m33ea 138 18 be be VB cord-021063-4y8m33ea 138 19 regulated regulate VBN cord-021063-4y8m33ea 138 20 by by IN cord-021063-4y8m33ea 138 21 means mean NNS cord-021063-4y8m33ea 138 22 of of IN cord-021063-4y8m33ea 138 23 tissue tissue NN cord-021063-4y8m33ea 138 24 - - HYPH cord-021063-4y8m33ea 138 25 specific specific JJ cord-021063-4y8m33ea 138 26 promoters promoter NNS cord-021063-4y8m33ea 138 27 ( ( -LRB- cord-021063-4y8m33ea 138 28 Hazinski Hazinski NNP cord-021063-4y8m33ea 138 29 et et NNP cord-021063-4y8m33ea 138 30 al al NNP cord-021063-4y8m33ea 138 31 . . NNP cord-021063-4y8m33ea 138 32 , , , cord-021063-4y8m33ea 138 33 1991 1991 CD cord-021063-4y8m33ea 138 34 ) ) -RRB- cord-021063-4y8m33ea 138 35 . . . cord-021063-4y8m33ea 139 1 Cell cell NN cord-021063-4y8m33ea 139 2 specific specific JJ cord-021063-4y8m33ea 139 3 promoters promoter NNS cord-021063-4y8m33ea 139 4 are be VBP cord-021063-4y8m33ea 139 5 not not RB cord-021063-4y8m33ea 139 6 available available JJ cord-021063-4y8m33ea 139 7 for for IN cord-021063-4y8m33ea 139 8 all all DT cord-021063-4y8m33ea 139 9 tissues tissue NNS cord-021063-4y8m33ea 139 10 , , , cord-021063-4y8m33ea 139 11 and and CC cord-021063-4y8m33ea 139 12 those those DT cord-021063-4y8m33ea 139 13 currently currently RB cord-021063-4y8m33ea 139 14 available available JJ cord-021063-4y8m33ea 139 15 are be VBP cord-021063-4y8m33ea 139 16 sometimes sometimes RB cord-021063-4y8m33ea 139 17 less less RBR cord-021063-4y8m33ea 139 18 specific specific JJ cord-021063-4y8m33ea 139 19 than than IN cord-021063-4y8m33ea 139 20 desired desire VBN cord-021063-4y8m33ea 139 21 . . . cord-021063-4y8m33ea 140 1 While while IN cord-021063-4y8m33ea 140 2 both both DT cord-021063-4y8m33ea 140 3 cationic cationic JJ cord-021063-4y8m33ea 140 4 liposomes liposome NNS cord-021063-4y8m33ea 140 5 and and CC cord-021063-4y8m33ea 140 6 retroviral retroviral NN cord-021063-4y8m33ea 140 7 gene gene NN cord-021063-4y8m33ea 140 8 delivery delivery NN cord-021063-4y8m33ea 140 9 vectors vector NNS cord-021063-4y8m33ea 140 10 lack lack VBP cord-021063-4y8m33ea 140 11 the the DT cord-021063-4y8m33ea 140 12 ability ability NN cord-021063-4y8m33ea 140 13 to to TO cord-021063-4y8m33ea 140 14 target target VB cord-021063-4y8m33ea 140 15 specific specific JJ cord-021063-4y8m33ea 140 16 cells cell NNS cord-021063-4y8m33ea 140 17 , , , cord-021063-4y8m33ea 140 18 the the DT cord-021063-4y8m33ea 140 19 lack lack NN cord-021063-4y8m33ea 140 20 of of IN cord-021063-4y8m33ea 140 21 length length NN cord-021063-4y8m33ea 140 22 constraints constraint NNS cord-021063-4y8m33ea 140 23 makes make VBZ cord-021063-4y8m33ea 140 24 tissue tissue NN cord-021063-4y8m33ea 140 25 - - HYPH cord-021063-4y8m33ea 140 26 specific specific JJ cord-021063-4y8m33ea 140 27 expression expression NN cord-021063-4y8m33ea 140 28 easier easy JJR cord-021063-4y8m33ea 140 29 to to TO cord-021063-4y8m33ea 140 30 achieve achieve VB cord-021063-4y8m33ea 140 31 using use VBG cord-021063-4y8m33ea 140 32 DNA dna NN cord-021063-4y8m33ea 140 33 - - HYPH cord-021063-4y8m33ea 140 34 lipid lipid NN cord-021063-4y8m33ea 140 35 complexes complex NNS cord-021063-4y8m33ea 140 36 as as IN cord-021063-4y8m33ea 140 37 compared compare VBN cord-021063-4y8m33ea 140 38 to to IN cord-021063-4y8m33ea 140 39 retroviruses retrovirus NNS cord-021063-4y8m33ea 140 40 . . . cord-021063-4y8m33ea 141 1 Ca2 Ca2 NNP cord-021063-4y8m33ea 141 2 + + CC cord-021063-4y8m33ea 142 1 /EDTA /EDTA NFP cord-021063-4y8m33ea 142 2 Chelation Chelation NNP cord-021063-4y8m33ea 142 3 . . . cord-021063-4y8m33ea 143 1 In in IN cord-021063-4y8m33ea 143 2 the the DT cord-021063-4y8m33ea 143 3 presence presence NN cord-021063-4y8m33ea 143 4 of of IN cord-021063-4y8m33ea 143 5 calcium calcium NN cord-021063-4y8m33ea 143 6 , , , cord-021063-4y8m33ea 143 7 small small JJ cord-021063-4y8m33ea 143 8 unilamellar unilamellar NNP cord-021063-4y8m33ea 143 9 vesicles vesicle NNS cord-021063-4y8m33ea 143 10 ( ( -LRB- cord-021063-4y8m33ea 143 11 SUVs suv NNS cord-021063-4y8m33ea 143 12 ) ) -RRB- cord-021063-4y8m33ea 143 13 composed compose VBN cord-021063-4y8m33ea 143 14 of of IN cord-021063-4y8m33ea 143 15 acidic acidic JJ cord-021063-4y8m33ea 143 16 phospholipids phospholipid NNS cord-021063-4y8m33ea 143 17 ( ( -LRB- cord-021063-4y8m33ea 143 18 typically typically RB cord-021063-4y8m33ea 143 19 phosphatidylserine phosphatidylserine NN cord-021063-4y8m33ea 143 20 ) ) -RRB- cord-021063-4y8m33ea 143 21 aggregate aggregate NN cord-021063-4y8m33ea 143 22 and and CC cord-021063-4y8m33ea 143 23 fuse fuse VB cord-021063-4y8m33ea 143 24 into into IN cord-021063-4y8m33ea 143 25 large large JJ cord-021063-4y8m33ea 143 26 cochleate cochleate NN cord-021063-4y8m33ea 143 27 structures structure NNS cord-021063-4y8m33ea 143 28 . . . cord-021063-4y8m33ea 144 1 When when WRB cord-021063-4y8m33ea 144 2 EDTA EDTA NNP cord-021063-4y8m33ea 144 3 is be VBZ cord-021063-4y8m33ea 144 4 added add VBN cord-021063-4y8m33ea 144 5 to to TO cord-021063-4y8m33ea 144 6 chelate chelate VB cord-021063-4y8m33ea 144 7 the the DT cord-021063-4y8m33ea 144 8 calcium calcium NN cord-021063-4y8m33ea 144 9 , , , cord-021063-4y8m33ea 144 10 these these DT cord-021063-4y8m33ea 144 11 structures structure NNS cord-021063-4y8m33ea 144 12 form form VBP cord-021063-4y8m33ea 144 13 large large JJ cord-021063-4y8m33ea 144 14 unilamellar unilamellar JJ cord-021063-4y8m33ea 144 15 vesicles vesicle NNS cord-021063-4y8m33ea 144 16 ( ( -LRB- cord-021063-4y8m33ea 144 17 LUVs LUVs NNP cord-021063-4y8m33ea 144 18 ) ) -RRB- cord-021063-4y8m33ea 145 1 ( ( -LRB- cord-021063-4y8m33ea 145 2 Papahadjopoulos Papahadjopoulos NNP cord-021063-4y8m33ea 145 3 et et NNP cord-021063-4y8m33ea 145 4 al al NNP cord-021063-4y8m33ea 145 5 . . NNP cord-021063-4y8m33ea 145 6 , , , cord-021063-4y8m33ea 145 7 1975 1975 CD cord-021063-4y8m33ea 145 8 ) ) -RRB- cord-021063-4y8m33ea 145 9 . . . cord-021063-4y8m33ea 146 1 In in IN cord-021063-4y8m33ea 146 2 the the DT cord-021063-4y8m33ea 146 3 process process NN cord-021063-4y8m33ea 146 4 , , , cord-021063-4y8m33ea 146 5 the the DT cord-021063-4y8m33ea 146 6 vesicles vesicle NNS cord-021063-4y8m33ea 146 7 encapsulate encapsulate VBP cord-021063-4y8m33ea 146 8 a a DT cord-021063-4y8m33ea 146 9 substantial substantial JJ cord-021063-4y8m33ea 146 10 fraction fraction NN cord-021063-4y8m33ea 146 11 of of IN cord-021063-4y8m33ea 146 12 the the DT cord-021063-4y8m33ea 146 13 surrounding surround VBG cord-021063-4y8m33ea 146 14 solvent solvent NN cord-021063-4y8m33ea 146 15 and and CC cord-021063-4y8m33ea 146 16 solutes solute NNS cord-021063-4y8m33ea 146 17 . . . cord-021063-4y8m33ea 147 1 If if IN cord-021063-4y8m33ea 147 2 DNA DNA NNP cord-021063-4y8m33ea 147 3 is be VBZ cord-021063-4y8m33ea 147 4 present present JJ cord-021063-4y8m33ea 147 5 , , , cord-021063-4y8m33ea 147 6 some some DT cord-021063-4y8m33ea 147 7 of of IN cord-021063-4y8m33ea 147 8 it -PRON- PRP cord-021063-4y8m33ea 147 9 becomes become VBZ cord-021063-4y8m33ea 147 10 encapsulated encapsulate VBN cord-021063-4y8m33ea 147 11 in in IN cord-021063-4y8m33ea 147 12 the the DT cord-021063-4y8m33ea 147 13 vesicles vesicle NNS cord-021063-4y8m33ea 147 14 . . . cord-021063-4y8m33ea 148 1 Two two CD cord-021063-4y8m33ea 148 2 advantages advantage NNS cord-021063-4y8m33ea 148 3 of of IN cord-021063-4y8m33ea 148 4 this this DT cord-021063-4y8m33ea 148 5 technique technique NN cord-021063-4y8m33ea 148 6 are be VBP cord-021063-4y8m33ea 148 7 : : : cord-021063-4y8m33ea 148 8 ( ( -LRB- cord-021063-4y8m33ea 148 9 i i NN cord-021063-4y8m33ea 148 10 ) ) -RRB- cord-021063-4y8m33ea 149 1 the the DT cord-021063-4y8m33ea 149 2 DNA DNA NNP cord-021063-4y8m33ea 149 3 is be VBZ cord-021063-4y8m33ea 149 4 not not RB cord-021063-4y8m33ea 149 5 exposed expose VBN cord-021063-4y8m33ea 149 6 to to IN cord-021063-4y8m33ea 149 7 harsh harsh JJ cord-021063-4y8m33ea 149 8 conditions condition NNS cord-021063-4y8m33ea 149 9 that that WDT cord-021063-4y8m33ea 149 10 would would MD cord-021063-4y8m33ea 149 11 degrade degrade VB cord-021063-4y8m33ea 149 12 it -PRON- PRP cord-021063-4y8m33ea 149 13 , , , cord-021063-4y8m33ea 149 14 and and CC cord-021063-4y8m33ea 149 15 ( ( -LRB- cord-021063-4y8m33ea 149 16 ii ii NN cord-021063-4y8m33ea 149 17 ) ) -RRB- cord-021063-4y8m33ea 150 1 the the DT cord-021063-4y8m33ea 150 2 entrapment entrapment NN cord-021063-4y8m33ea 150 3 is be VBZ cord-021063-4y8m33ea 150 4 relatively relatively RB cord-021063-4y8m33ea 150 5 efficient efficient JJ cord-021063-4y8m33ea 150 6 . . . cord-021063-4y8m33ea 151 1 However however RB cord-021063-4y8m33ea 151 2 , , , cord-021063-4y8m33ea 151 3 the the DT cord-021063-4y8m33ea 151 4 requirement requirement NN cord-021063-4y8m33ea 151 5 for for IN cord-021063-4y8m33ea 151 6 phosphatidylserine phosphatidylserine NN cord-021063-4y8m33ea 151 7 makes make VBZ cord-021063-4y8m33ea 151 8 this this DT cord-021063-4y8m33ea 151 9 technique technique NN cord-021063-4y8m33ea 151 10 impractical impractical JJ cord-021063-4y8m33ea 151 11 for for IN cord-021063-4y8m33ea 151 12 most most JJS cord-021063-4y8m33ea 151 13 in in IN cord-021063-4y8m33ea 151 14 vivo vivo NN cord-021063-4y8m33ea 151 15 applications application NNS cord-021063-4y8m33ea 151 16 , , , cord-021063-4y8m33ea 151 17 with with IN cord-021063-4y8m33ea 151 18 the the DT cord-021063-4y8m33ea 151 19 exception exception NN cord-021063-4y8m33ea 151 20 of of IN cord-021063-4y8m33ea 151 21 transfecting transfecting NN cord-021063-4y8m33ea 151 22 macrophages macrophage NNS cord-021063-4y8m33ea 151 23 which which WDT cord-021063-4y8m33ea 151 24 have have VBP cord-021063-4y8m33ea 151 25 cell cell NN cord-021063-4y8m33ea 151 26 surface surface NN cord-021063-4y8m33ea 151 27 receptors receptor NNS cord-021063-4y8m33ea 151 28 for for IN cord-021063-4y8m33ea 151 29 phosphatidylserine phosphatidylserine NN cord-021063-4y8m33ea 151 30 ( ( -LRB- cord-021063-4y8m33ea 151 31 PS PS NNP cord-021063-4y8m33ea 151 32 ) ) -RRB- cord-021063-4y8m33ea 151 33 . . . cord-021063-4y8m33ea 152 1 Detergent Detergent NNP cord-021063-4y8m33ea 152 2 Dialysis Dialysis NNP cord-021063-4y8m33ea 152 3 ( ( -LRB- cord-021063-4y8m33ea 152 4 and and CC cord-021063-4y8m33ea 152 5 Virosomes Virosomes NNP cord-021063-4y8m33ea 152 6 ) ) -RRB- cord-021063-4y8m33ea 152 7 . . . cord-021063-4y8m33ea 153 1 When when WRB cord-021063-4y8m33ea 153 2 membranes membrane NNS cord-021063-4y8m33ea 153 3 are be VBP cord-021063-4y8m33ea 153 4 mixed mix VBN cord-021063-4y8m33ea 153 5 with with IN cord-021063-4y8m33ea 153 6 detergents detergent NNS cord-021063-4y8m33ea 153 7 at at IN cord-021063-4y8m33ea 153 8 concentrations concentration NNS cord-021063-4y8m33ea 153 9 above above IN cord-021063-4y8m33ea 153 10 their -PRON- PRP$ cord-021063-4y8m33ea 153 11 critical critical JJ cord-021063-4y8m33ea 153 12 mixed mixed JJ cord-021063-4y8m33ea 153 13 micellar micellar JJ cord-021063-4y8m33ea 153 14 concentration concentration NN cord-021063-4y8m33ea 153 15 ( ( -LRB- cord-021063-4y8m33ea 153 16 CMMC CMMC NNP cord-021063-4y8m33ea 153 17 ) ) -RRB- cord-021063-4y8m33ea 153 18 , , , cord-021063-4y8m33ea 153 19 they -PRON- PRP cord-021063-4y8m33ea 153 20 combine combine VBP cord-021063-4y8m33ea 153 21 with with IN cord-021063-4y8m33ea 153 22 the the DT cord-021063-4y8m33ea 153 23 membrane membrane NN cord-021063-4y8m33ea 153 24 's 's POS cord-021063-4y8m33ea 153 25 phospholipids phospholipid NNS cord-021063-4y8m33ea 153 26 and and CC cord-021063-4y8m33ea 153 27 proteins protein NNS cord-021063-4y8m33ea 153 28 to to TO cord-021063-4y8m33ea 153 29 form form VB cord-021063-4y8m33ea 153 30 mixed mixed JJ cord-021063-4y8m33ea 153 31 micelles micelle NNS cord-021063-4y8m33ea 153 32 . . . cord-021063-4y8m33ea 154 1 Because because IN cord-021063-4y8m33ea 154 2 detergents detergent NNS cord-021063-4y8m33ea 154 3 are be VBP cord-021063-4y8m33ea 154 4 relatively relatively RB cord-021063-4y8m33ea 154 5 water water NN cord-021063-4y8m33ea 154 6 soluble soluble JJ cord-021063-4y8m33ea 154 7 , , , cord-021063-4y8m33ea 154 8 they -PRON- PRP cord-021063-4y8m33ea 154 9 can can MD cord-021063-4y8m33ea 154 10 be be VB cord-021063-4y8m33ea 154 11 removed remove VBN cord-021063-4y8m33ea 154 12 from from IN cord-021063-4y8m33ea 154 13 the the DT cord-021063-4y8m33ea 154 14 mixed mixed JJ cord-021063-4y8m33ea 154 15 micelles micelle NNS cord-021063-4y8m33ea 154 16 by by IN cord-021063-4y8m33ea 154 17 dialysis dialysis NN cord-021063-4y8m33ea 154 18 . . . cord-021063-4y8m33ea 155 1 When when WRB cord-021063-4y8m33ea 155 2 their -PRON- PRP$ cord-021063-4y8m33ea 155 3 concentration concentration NN cord-021063-4y8m33ea 155 4 in in IN cord-021063-4y8m33ea 155 5 the the DT cord-021063-4y8m33ea 155 6 micelles micelle NNS cord-021063-4y8m33ea 155 7 falls fall VBZ cord-021063-4y8m33ea 155 8 below below IN cord-021063-4y8m33ea 155 9 the the DT cord-021063-4y8m33ea 155 10 CMMC CMMC NNP cord-021063-4y8m33ea 155 11 , , , cord-021063-4y8m33ea 155 12 membrane membrane NN cord-021063-4y8m33ea 155 13 bilayers bilayer NNS cord-021063-4y8m33ea 155 14 regenerate regenerate VBP cord-021063-4y8m33ea 155 15 and and CC cord-021063-4y8m33ea 155 16 form form NN cord-021063-4y8m33ea 155 17 liposomes liposome NNS cord-021063-4y8m33ea 155 18 . . . cord-021063-4y8m33ea 156 1 Enveloped envelop VBN cord-021063-4y8m33ea 156 2 viruses virus NNS cord-021063-4y8m33ea 156 3 have have VBP cord-021063-4y8m33ea 156 4 membrane membrane NN cord-021063-4y8m33ea 156 5 proteins protein NNS cord-021063-4y8m33ea 156 6 that that WDT cord-021063-4y8m33ea 156 7 promote promote VBP cord-021063-4y8m33ea 156 8 the the DT cord-021063-4y8m33ea 156 9 fusion fusion NN cord-021063-4y8m33ea 156 10 of of IN cord-021063-4y8m33ea 156 11 the the DT cord-021063-4y8m33ea 156 12 viral viral JJ cord-021063-4y8m33ea 156 13 membrane membrane NN cord-021063-4y8m33ea 156 14 with with IN cord-021063-4y8m33ea 156 15 cellular cellular JJ cord-021063-4y8m33ea 156 16 membranes membrane NNS cord-021063-4y8m33ea 156 17 . . . cord-021063-4y8m33ea 157 1 When when WRB cord-021063-4y8m33ea 157 2 an an DT cord-021063-4y8m33ea 157 3 enveloped envelop VBN cord-021063-4y8m33ea 157 4 virus virus NN cord-021063-4y8m33ea 157 5 fuses fuse VBZ cord-021063-4y8m33ea 157 6 to to IN cord-021063-4y8m33ea 157 7 a a DT cord-021063-4y8m33ea 157 8 cell cell NN cord-021063-4y8m33ea 157 9 , , , cord-021063-4y8m33ea 157 10 the the DT cord-021063-4y8m33ea 157 11 nucleocapsid nucleocapsid NN cord-021063-4y8m33ea 157 12 is be VBZ cord-021063-4y8m33ea 157 13 released release VBN cord-021063-4y8m33ea 157 14 into into IN cord-021063-4y8m33ea 157 15 the the DT cord-021063-4y8m33ea 157 16 cytoplasm cytoplasm NN cord-021063-4y8m33ea 157 17 , , , cord-021063-4y8m33ea 157 18 and and CC cord-021063-4y8m33ea 157 19 the the DT cord-021063-4y8m33ea 157 20 infection infection NN cord-021063-4y8m33ea 157 21 proceeds proceed VBZ cord-021063-4y8m33ea 157 22 . . . cord-021063-4y8m33ea 158 1 Detergent detergent NN cord-021063-4y8m33ea 158 2 solubilization solubilization NN cord-021063-4y8m33ea 158 3 of of IN cord-021063-4y8m33ea 158 4 enveloped enveloped JJ cord-021063-4y8m33ea 158 5 viruses virus NNS cord-021063-4y8m33ea 158 6 produces produce VBZ cord-021063-4y8m33ea 158 7 a a DT cord-021063-4y8m33ea 158 8 micellar micellar JJ cord-021063-4y8m33ea 158 9 mixture mixture NN cord-021063-4y8m33ea 158 10 containing contain VBG cord-021063-4y8m33ea 158 11 detergent detergent NN cord-021063-4y8m33ea 158 12 , , , cord-021063-4y8m33ea 158 13 viral viral JJ cord-021063-4y8m33ea 158 14 phospholipids phospholipid NNS cord-021063-4y8m33ea 158 15 , , , cord-021063-4y8m33ea 158 16 and and CC cord-021063-4y8m33ea 158 17 viral viral JJ cord-021063-4y8m33ea 158 18 membrane membrane NN cord-021063-4y8m33ea 158 19 proteins protein NNS cord-021063-4y8m33ea 158 20 . . . cord-021063-4y8m33ea 159 1 Dialysis dialysis NN cord-021063-4y8m33ea 159 2 of of IN cord-021063-4y8m33ea 159 3 these these DT cord-021063-4y8m33ea 159 4 detergent detergent NN cord-021063-4y8m33ea 159 5 mixtures mixture NNS cord-021063-4y8m33ea 159 6 results result NNS cord-021063-4y8m33ea 159 7 in in IN cord-021063-4y8m33ea 159 8 the the DT cord-021063-4y8m33ea 159 9 production production NN cord-021063-4y8m33ea 159 10 of of IN cord-021063-4y8m33ea 159 11 liposomes liposome NNS cord-021063-4y8m33ea 159 12 that that WDT cord-021063-4y8m33ea 159 13 are be VBP cord-021063-4y8m33ea 159 14 often often RB cord-021063-4y8m33ea 159 15 called call VBN cord-021063-4y8m33ea 159 16 virosomes virosome NNS cord-021063-4y8m33ea 159 17 to to TO cord-021063-4y8m33ea 159 18 indicate indicate VB cord-021063-4y8m33ea 159 19 the the DT cord-021063-4y8m33ea 159 20 presence presence NN cord-021063-4y8m33ea 159 21 of of IN cord-021063-4y8m33ea 159 22 viral viral JJ cord-021063-4y8m33ea 159 23 proteins protein NNS cord-021063-4y8m33ea 159 24 . . . cord-021063-4y8m33ea 160 1 If if IN cord-021063-4y8m33ea 160 2 the the DT cord-021063-4y8m33ea 160 3 dialysis dialysis NN cord-021063-4y8m33ea 160 4 is be VBZ cord-021063-4y8m33ea 160 5 performed perform VBN cord-021063-4y8m33ea 160 6 properly properly RB cord-021063-4y8m33ea 160 7 , , , cord-021063-4y8m33ea 160 8 the the DT cord-021063-4y8m33ea 160 9 fusion fusion NN cord-021063-4y8m33ea 160 10 proteins protein NNS cord-021063-4y8m33ea 160 11 of of IN cord-021063-4y8m33ea 160 12 many many JJ cord-021063-4y8m33ea 160 13 viruses virus NNS cord-021063-4y8m33ea 160 14 can can MD cord-021063-4y8m33ea 160 15 be be VB cord-021063-4y8m33ea 160 16 reconstituted reconstitute VBN cord-021063-4y8m33ea 160 17 in in IN cord-021063-4y8m33ea 160 18 an an DT cord-021063-4y8m33ea 160 19 active active JJ cord-021063-4y8m33ea 160 20 conformation conformation NN cord-021063-4y8m33ea 160 21 ( ( -LRB- cord-021063-4y8m33ea 160 22 White White NNP cord-021063-4y8m33ea 160 23 et et FW cord-021063-4y8m33ea 160 24 al al NNP cord-021063-4y8m33ea 160 25 . . NNP cord-021063-4y8m33ea 160 26 , , , cord-021063-4y8m33ea 160 27 1983 1983 CD cord-021063-4y8m33ea 160 28 ) ) -RRB- cord-021063-4y8m33ea 160 29 . . . cord-021063-4y8m33ea 161 1 Viral viral JJ cord-021063-4y8m33ea 161 2 fusion fusion NN cord-021063-4y8m33ea 161 3 proteins protein NNS cord-021063-4y8m33ea 161 4 having have VBG cord-021063-4y8m33ea 161 5 a a DT cord-021063-4y8m33ea 161 6 variety variety NN cord-021063-4y8m33ea 161 7 of of IN cord-021063-4y8m33ea 161 8 different different JJ cord-021063-4y8m33ea 161 9 characteristics characteristic NNS cord-021063-4y8m33ea 161 10 have have VBP cord-021063-4y8m33ea 161 11 been be VBN cord-021063-4y8m33ea 161 12 identified identify VBN cord-021063-4y8m33ea 161 13 . . . cord-021063-4y8m33ea 162 1 For for IN cord-021063-4y8m33ea 162 2 example example NN cord-021063-4y8m33ea 162 3 , , , cord-021063-4y8m33ea 162 4 some some DT cord-021063-4y8m33ea 162 5 are be VBP cord-021063-4y8m33ea 162 6 only only RB cord-021063-4y8m33ea 162 7 active active JJ cord-021063-4y8m33ea 162 8 at at IN cord-021063-4y8m33ea 162 9 low low JJ cord-021063-4y8m33ea 162 10 pH ph NN cord-021063-4y8m33ea 162 11 and and CC cord-021063-4y8m33ea 162 12 fuse fuse VB cord-021063-4y8m33ea 162 13 with with IN cord-021063-4y8m33ea 162 14 endosomal endosomal NNP cord-021063-4y8m33ea 162 15 membranes membrane NNS cord-021063-4y8m33ea 162 16 , , , cord-021063-4y8m33ea 162 17 while while IN cord-021063-4y8m33ea 162 18 others other NNS cord-021063-4y8m33ea 162 19 are be VBP cord-021063-4y8m33ea 162 20 active active JJ cord-021063-4y8m33ea 162 21 at at IN cord-021063-4y8m33ea 162 22 physiological physiological JJ cord-021063-4y8m33ea 162 23 pH ph NN cord-021063-4y8m33ea 162 24 and and CC cord-021063-4y8m33ea 162 25 fuse fuse VB cord-021063-4y8m33ea 162 26 to to IN cord-021063-4y8m33ea 162 27 the the DT cord-021063-4y8m33ea 162 28 plasma plasma NN cord-021063-4y8m33ea 162 29 membrane membrane NN cord-021063-4y8m33ea 162 30 . . . cord-021063-4y8m33ea 163 1 Some some DT cord-021063-4y8m33ea 163 2 viral viral JJ cord-021063-4y8m33ea 163 3 fusion fusion NN cord-021063-4y8m33ea 163 4 proteins protein NNS cord-021063-4y8m33ea 163 5 , , , cord-021063-4y8m33ea 163 6 such such JJ cord-021063-4y8m33ea 163 7 as as IN cord-021063-4y8m33ea 163 8 the the DT cord-021063-4y8m33ea 163 9 HA HA NNP cord-021063-4y8m33ea 163 10 protein protein NN cord-021063-4y8m33ea 163 11 of of IN cord-021063-4y8m33ea 163 12 influenza influenza NN cord-021063-4y8m33ea 163 13 , , , cord-021063-4y8m33ea 163 14 bind bind VB cord-021063-4y8m33ea 163 15 to to IN cord-021063-4y8m33ea 163 16 specific specific JJ cord-021063-4y8m33ea 163 17 receptors receptor NNS cord-021063-4y8m33ea 163 18 before before IN cord-021063-4y8m33ea 163 19 fusion fusion NN cord-021063-4y8m33ea 163 20 . . . cord-021063-4y8m33ea 164 1 A a DT cord-021063-4y8m33ea 164 2 few few JJ cord-021063-4y8m33ea 164 3 viral viral JJ cord-021063-4y8m33ea 164 4 fusion fusion NN cord-021063-4y8m33ea 164 5 proteins protein NNS cord-021063-4y8m33ea 164 6 will will MD cord-021063-4y8m33ea 164 7 only only RB cord-021063-4y8m33ea 164 8 promote promote VB cord-021063-4y8m33ea 164 9 fusion fusion NN cord-021063-4y8m33ea 164 10 to to TO cord-021063-4y8m33ea 164 11 target target VB cord-021063-4y8m33ea 164 12 membranes membrane NNS cord-021063-4y8m33ea 164 13 containing contain VBG cord-021063-4y8m33ea 164 14 a a DT cord-021063-4y8m33ea 164 15 specific specific JJ cord-021063-4y8m33ea 164 16 mixture mixture NN cord-021063-4y8m33ea 164 17 of of IN cord-021063-4y8m33ea 164 18 phospholipids phospholipid NNS cord-021063-4y8m33ea 164 19 ( ( -LRB- cord-021063-4y8m33ea 164 20 Cervin Cervin NNP cord-021063-4y8m33ea 164 21 and and CC cord-021063-4y8m33ea 164 22 Anderson Anderson NNP cord-021063-4y8m33ea 164 23 , , , cord-021063-4y8m33ea 164 24 1991 1991 CD cord-021063-4y8m33ea 164 25 ; ; : cord-021063-4y8m33ea 164 26 Nussbaum Nussbaum NNP cord-021063-4y8m33ea 164 27 et et NNP cord-021063-4y8m33ea 164 28 al al NNP cord-021063-4y8m33ea 164 29 . . NNP cord-021063-4y8m33ea 164 30 , , , cord-021063-4y8m33ea 164 31 1992 1992 CD cord-021063-4y8m33ea 164 32 ) ) -RRB- cord-021063-4y8m33ea 164 33 . . . cord-021063-4y8m33ea 165 1 The the DT cord-021063-4y8m33ea 165 2 major major JJ cord-021063-4y8m33ea 165 3 advantage advantage NN cord-021063-4y8m33ea 165 4 of of IN cord-021063-4y8m33ea 165 5 detergent detergent NN cord-021063-4y8m33ea 165 6 dialysis dialysis NN cord-021063-4y8m33ea 165 7 is be VBZ cord-021063-4y8m33ea 165 8 that that IN cord-021063-4y8m33ea 165 9 it -PRON- PRP cord-021063-4y8m33ea 165 10 is be VBZ cord-021063-4y8m33ea 165 11 very very RB cord-021063-4y8m33ea 165 12 gentle gentle JJ cord-021063-4y8m33ea 165 13 since since IN cord-021063-4y8m33ea 165 14 no no DT cord-021063-4y8m33ea 165 15 sonication sonication NN cord-021063-4y8m33ea 165 16 , , , cord-021063-4y8m33ea 165 17 vortexing vortexing NN cord-021063-4y8m33ea 165 18 , , , cord-021063-4y8m33ea 165 19 or or CC cord-021063-4y8m33ea 165 20 organic organic JJ cord-021063-4y8m33ea 165 21 solvent solvent NN cord-021063-4y8m33ea 165 22 is be VBZ cord-021063-4y8m33ea 165 23 used use VBN cord-021063-4y8m33ea 165 24 . . . cord-021063-4y8m33ea 166 1 This this DT cord-021063-4y8m33ea 166 2 results result VBZ cord-021063-4y8m33ea 166 3 in in IN cord-021063-4y8m33ea 166 4 only only RB cord-021063-4y8m33ea 166 5 a a DT cord-021063-4y8m33ea 166 6 small small JJ cord-021063-4y8m33ea 166 7 amount amount NN cord-021063-4y8m33ea 166 8 of of IN cord-021063-4y8m33ea 166 9 DNA dna NN cord-021063-4y8m33ea 166 10 fragmentation fragmentation NN cord-021063-4y8m33ea 166 11 during during IN cord-021063-4y8m33ea 166 12 encapsulation encapsulation NN cord-021063-4y8m33ea 166 13 . . . cord-021063-4y8m33ea 167 1 Unfortunately unfortunately RB cord-021063-4y8m33ea 167 2 , , , cord-021063-4y8m33ea 167 3 the the DT cord-021063-4y8m33ea 167 4 efficiency efficiency NN cord-021063-4y8m33ea 167 5 of of IN cord-021063-4y8m33ea 167 6 entrapment entrapment NN cord-021063-4y8m33ea 167 7 is be VBZ cord-021063-4y8m33ea 167 8 very very RB cord-021063-4y8m33ea 167 9 low low JJ cord-021063-4y8m33ea 167 10 , , , cord-021063-4y8m33ea 167 11 causing cause VBG cord-021063-4y8m33ea 167 12 much much JJ cord-021063-4y8m33ea 167 13 of of IN cord-021063-4y8m33ea 167 14 the the DT cord-021063-4y8m33ea 167 15 DNA dna NN cord-021063-4y8m33ea 167 16 to to TO cord-021063-4y8m33ea 167 17 be be VB cord-021063-4y8m33ea 167 18 wasted waste VBN cord-021063-4y8m33ea 167 19 and and CC cord-021063-4y8m33ea 167 20 resulting result VBG cord-021063-4y8m33ea 167 21 in in IN cord-021063-4y8m33ea 167 22 a a DT cord-021063-4y8m33ea 167 23 high high JJ cord-021063-4y8m33ea 167 24 fraction fraction NN cord-021063-4y8m33ea 167 25 of of IN cord-021063-4y8m33ea 167 26 empty empty JJ cord-021063-4y8m33ea 167 27 liposomes liposome NNS cord-021063-4y8m33ea 167 28 being be VBG cord-021063-4y8m33ea 167 29 formed form VBN cord-021063-4y8m33ea 167 30 . . . cord-021063-4y8m33ea 168 1 Loyter Loyter NNP cord-021063-4y8m33ea 168 2 and and CC cord-021063-4y8m33ea 168 3 co co NNS cord-021063-4y8m33ea 168 4 - - NNS cord-021063-4y8m33ea 168 5 workers worker NNS cord-021063-4y8m33ea 168 6 have have VBP cord-021063-4y8m33ea 168 7 fused fuse VBN cord-021063-4y8m33ea 168 8 DNA dna NN cord-021063-4y8m33ea 168 9 - - HYPH cord-021063-4y8m33ea 168 10 containing containing NN cord-021063-4y8m33ea 168 11 liposomes liposome NNS cord-021063-4y8m33ea 168 12 with with IN cord-021063-4y8m33ea 168 13 cells cell NNS cord-021063-4y8m33ea 168 14 by by IN cord-021063-4y8m33ea 168 15 making make VBG cord-021063-4y8m33ea 168 16 empty empty JJ cord-021063-4y8m33ea 168 17 virosomes virosome NNS cord-021063-4y8m33ea 168 18 and and CC cord-021063-4y8m33ea 168 19 DNA dna NN cord-021063-4y8m33ea 168 20 - - HYPH cord-021063-4y8m33ea 168 21 containing containing NN cord-021063-4y8m33ea 168 22 liposomes liposome NNS cord-021063-4y8m33ea 168 23 separately separately RB cord-021063-4y8m33ea 168 24 , , , cord-021063-4y8m33ea 168 25 and and CC cord-021063-4y8m33ea 168 26 then then RB cord-021063-4y8m33ea 168 27 fusing fuse VBG cord-021063-4y8m33ea 168 28 the the DT cord-021063-4y8m33ea 168 29 two two CD cord-021063-4y8m33ea 168 30 populations population NNS cord-021063-4y8m33ea 168 31 of of IN cord-021063-4y8m33ea 168 32 vesicles vesicle NNS cord-021063-4y8m33ea 168 33 in in IN cord-021063-4y8m33ea 168 34 the the DT cord-021063-4y8m33ea 168 35 presence presence NN cord-021063-4y8m33ea 168 36 of of IN cord-021063-4y8m33ea 168 37 target target NN cord-021063-4y8m33ea 168 38 cells cell NNS cord-021063-4y8m33ea 168 39 ( ( -LRB- cord-021063-4y8m33ea 168 40 Lapidot Lapidot NNP cord-021063-4y8m33ea 168 41 and and CC cord-021063-4y8m33ea 168 42 Loyter Loyter NNP cord-021063-4y8m33ea 168 43 , , , cord-021063-4y8m33ea 168 44 1990 1990 CD cord-021063-4y8m33ea 168 45 ) ) -RRB- cord-021063-4y8m33ea 168 46 . . . cord-021063-4y8m33ea 169 1 To to IN cord-021063-4y8m33ea 169 2 date date NN cord-021063-4y8m33ea 169 3 , , , cord-021063-4y8m33ea 169 4 this this DT cord-021063-4y8m33ea 169 5 technique technique NN cord-021063-4y8m33ea 169 6 has have VBZ cord-021063-4y8m33ea 169 7 not not RB cord-021063-4y8m33ea 169 8 been be VBN cord-021063-4y8m33ea 169 9 used use VBN cord-021063-4y8m33ea 169 10 in in IN cord-021063-4y8m33ea 169 11 vivo vivo NN cord-021063-4y8m33ea 169 12 . . . cord-021063-4y8m33ea 170 1 Reverse Reverse NNP cord-021063-4y8m33ea 170 2 - - HYPH cord-021063-4y8m33ea 170 3 Phase phase NN cord-021063-4y8m33ea 170 4 Evaporation evaporation NN cord-021063-4y8m33ea 170 5 . . . cord-021063-4y8m33ea 171 1 Currently currently RB cord-021063-4y8m33ea 171 2 , , , cord-021063-4y8m33ea 171 3 the the DT cord-021063-4y8m33ea 171 4 highest high JJS cord-021063-4y8m33ea 171 5 DNA dna NN cord-021063-4y8m33ea 171 6 entrapment entrapment NN cord-021063-4y8m33ea 171 7 efficiencies efficiency NNS cord-021063-4y8m33ea 171 8 can can MD cord-021063-4y8m33ea 171 9 be be VB cord-021063-4y8m33ea 171 10 achieved achieve VBN cord-021063-4y8m33ea 171 11 when when WRB cord-021063-4y8m33ea 171 12 vesicles vesicle NNS cord-021063-4y8m33ea 171 13 ( ( -LRB- cord-021063-4y8m33ea 171 14 REVs rev NNS cord-021063-4y8m33ea 171 15 ) ) -RRB- cord-021063-4y8m33ea 171 16 are be VBP cord-021063-4y8m33ea 171 17 prepared prepare VBN cord-021063-4y8m33ea 171 18 by by IN cord-021063-4y8m33ea 171 19 reverse reverse JJ cord-021063-4y8m33ea 171 20 - - HYPH cord-021063-4y8m33ea 171 21 phase phase NN cord-021063-4y8m33ea 171 22 evaporation evaporation NN cord-021063-4y8m33ea 172 1 ( ( -LRB- cord-021063-4y8m33ea 172 2 Fraley Fraley NNP cord-021063-4y8m33ea 172 3 et et NNP cord-021063-4y8m33ea 172 4 al al NNP cord-021063-4y8m33ea 172 5 . . NNP cord-021063-4y8m33ea 172 6 , , , cord-021063-4y8m33ea 172 7 1980 1980 CD cord-021063-4y8m33ea 172 8 ) ) -RRB- cord-021063-4y8m33ea 172 9 . . . cord-021063-4y8m33ea 173 1 REVs rev NNS cord-021063-4y8m33ea 173 2 are be VBP cord-021063-4y8m33ea 173 3 prepared prepare VBN cord-021063-4y8m33ea 173 4 by by IN cord-021063-4y8m33ea 173 5 bath bath NN cord-021063-4y8m33ea 173 6 sonication sonication NN cord-021063-4y8m33ea 173 7 of of IN cord-021063-4y8m33ea 173 8 a a DT cord-021063-4y8m33ea 173 9 mixture mixture NN cord-021063-4y8m33ea 173 10 of of IN cord-021063-4y8m33ea 173 11 lipid lipid NN cord-021063-4y8m33ea 173 12 , , , cord-021063-4y8m33ea 173 13 DNA dna NN cord-021063-4y8m33ea 173 14 , , , cord-021063-4y8m33ea 173 15 ether ether NN cord-021063-4y8m33ea 173 16 , , , cord-021063-4y8m33ea 173 17 and and CC cord-021063-4y8m33ea 173 18 buffered buffer VBN cord-021063-4y8m33ea 173 19 saline saline NN cord-021063-4y8m33ea 173 20 , , , cord-021063-4y8m33ea 173 21 followed follow VBN cord-021063-4y8m33ea 173 22 by by IN cord-021063-4y8m33ea 173 23 evaporation evaporation NN cord-021063-4y8m33ea 173 24 of of IN cord-021063-4y8m33ea 173 25 the the DT cord-021063-4y8m33ea 173 26 ether ether NN cord-021063-4y8m33ea 173 27 to to TO cord-021063-4y8m33ea 173 28 form form VB cord-021063-4y8m33ea 173 29 a a DT cord-021063-4y8m33ea 173 30 paste paste NN cord-021063-4y8m33ea 173 31 of of IN cord-021063-4y8m33ea 173 32 phospholipid phospholipid NN cord-021063-4y8m33ea 173 33 inverted invert VBN cord-021063-4y8m33ea 173 34 monolayers monolayer NNS cord-021063-4y8m33ea 173 35 surrounding surround VBG cord-021063-4y8m33ea 173 36 aqueous aqueous JJ cord-021063-4y8m33ea 173 37 droplets droplet NNS cord-021063-4y8m33ea 173 38 . . . cord-021063-4y8m33ea 174 1 These these DT cord-021063-4y8m33ea 174 2 are be VBP cord-021063-4y8m33ea 174 3 resolved resolve VBN cord-021063-4y8m33ea 174 4 into into IN cord-021063-4y8m33ea 174 5 liposomes liposome NNS cord-021063-4y8m33ea 174 6 by by IN cord-021063-4y8m33ea 174 7 vortexing vortexe VBG cord-021063-4y8m33ea 174 8 the the DT cord-021063-4y8m33ea 174 9 paste paste NN cord-021063-4y8m33ea 174 10 . . . cord-021063-4y8m33ea 175 1 Encapsulation encapsulation NN cord-021063-4y8m33ea 175 2 efficiency efficiency NN cord-021063-4y8m33ea 175 3 is be VBZ cord-021063-4y8m33ea 175 4 high high JJ cord-021063-4y8m33ea 175 5 ( ( -LRB- cord-021063-4y8m33ea 175 6 up up IN cord-021063-4y8m33ea 175 7 to to TO cord-021063-4y8m33ea 175 8 40 40 CD cord-021063-4y8m33ea 175 9 or or CC cord-021063-4y8m33ea 175 10 50 50 CD cord-021063-4y8m33ea 175 11 % % NN cord-021063-4y8m33ea 175 12 ) ) -RRB- cord-021063-4y8m33ea 175 13 because because IN cord-021063-4y8m33ea 175 14 there there EX cord-021063-4y8m33ea 175 15 is be VBZ cord-021063-4y8m33ea 175 16 only only RB cord-021063-4y8m33ea 175 17 a a DT cord-021063-4y8m33ea 175 18 small small JJ cord-021063-4y8m33ea 175 19 amount amount NN cord-021063-4y8m33ea 175 20 of of IN cord-021063-4y8m33ea 175 21 aqueous aqueous JJ cord-021063-4y8m33ea 175 22 buffer buffer NN cord-021063-4y8m33ea 175 23 present present JJ cord-021063-4y8m33ea 175 24 in in IN cord-021063-4y8m33ea 175 25 relation relation NN cord-021063-4y8m33ea 175 26 to to IN cord-021063-4y8m33ea 175 27 the the DT cord-021063-4y8m33ea 175 28 amount amount NN cord-021063-4y8m33ea 175 29 of of IN cord-021063-4y8m33ea 175 30 lipid lipid NN cord-021063-4y8m33ea 175 31 . . . cord-021063-4y8m33ea 176 1 Presumably presumably RB cord-021063-4y8m33ea 176 2 , , , cord-021063-4y8m33ea 176 3 DNA dna NN cord-021063-4y8m33ea 176 4 molecules molecule NNS cord-021063-4y8m33ea 176 5 present present JJ cord-021063-4y8m33ea 176 6 in in IN cord-021063-4y8m33ea 176 7 the the DT cord-021063-4y8m33ea 176 8 buffer buffer NN cord-021063-4y8m33ea 176 9 are be VBP cord-021063-4y8m33ea 176 10 forced force VBN cord-021063-4y8m33ea 176 11 to to TO cord-021063-4y8m33ea 176 12 curl curl VB cord-021063-4y8m33ea 176 13 up up RP cord-021063-4y8m33ea 176 14 in in IN cord-021063-4y8m33ea 176 15 small small JJ cord-021063-4y8m33ea 176 16 aqueous aqueous JJ cord-021063-4y8m33ea 176 17 droplets droplet NNS cord-021063-4y8m33ea 176 18 , , , cord-021063-4y8m33ea 176 19 a a DT cord-021063-4y8m33ea 176 20 conformation conformation NN cord-021063-4y8m33ea 176 21 that that WDT cord-021063-4y8m33ea 176 22 is be VBZ cord-021063-4y8m33ea 176 23 easily easily RB cord-021063-4y8m33ea 176 24 entrapped entrap VBN cord-021063-4y8m33ea 176 25 ( ( -LRB- cord-021063-4y8m33ea 176 26 Szelei Szelei NNP cord-021063-4y8m33ea 176 27 and and CC cord-021063-4y8m33ea 176 28 Duda Duda NNP cord-021063-4y8m33ea 176 29 , , , cord-021063-4y8m33ea 176 30 1989 1989 CD cord-021063-4y8m33ea 176 31 ) ) -RRB- cord-021063-4y8m33ea 176 32 . . . cord-021063-4y8m33ea 177 1 Because because IN cord-021063-4y8m33ea 177 2 the the DT cord-021063-4y8m33ea 177 3 size size NN cord-021063-4y8m33ea 177 4 distribution distribution NN cord-021063-4y8m33ea 177 5 of of IN cord-021063-4y8m33ea 177 6 the the DT cord-021063-4y8m33ea 177 7 REVs rev NNS cord-021063-4y8m33ea 177 8 is be VBZ cord-021063-4y8m33ea 177 9 heterogeneous heterogeneous JJ cord-021063-4y8m33ea 177 10 and and CC cord-021063-4y8m33ea 177 11 hard hard JJ cord-021063-4y8m33ea 177 12 to to TO cord-021063-4y8m33ea 177 13 control control VB cord-021063-4y8m33ea 177 14 , , , cord-021063-4y8m33ea 177 15 they -PRON- PRP cord-021063-4y8m33ea 177 16 are be VBP cord-021063-4y8m33ea 177 17 often often RB cord-021063-4y8m33ea 177 18 sized size VBN cord-021063-4y8m33ea 177 19 by by IN cord-021063-4y8m33ea 177 20 extrusion extrusion NN cord-021063-4y8m33ea 177 21 through through IN cord-021063-4y8m33ea 177 22 a a DT cord-021063-4y8m33ea 177 23 filter filter NN cord-021063-4y8m33ea 177 24 before before IN cord-021063-4y8m33ea 177 25 use use NN cord-021063-4y8m33ea 177 26 . . . cord-021063-4y8m33ea 178 1 Extrusion extrusion NN cord-021063-4y8m33ea 178 2 . . . cord-021063-4y8m33ea 179 1 Multilamellar multilamellar JJ cord-021063-4y8m33ea 179 2 vesicles vesicle NNS cord-021063-4y8m33ea 179 3 formed form VBN cord-021063-4y8m33ea 179 4 by by IN cord-021063-4y8m33ea 179 5 vortexing vortexe VBG cord-021063-4y8m33ea 179 6 a a DT cord-021063-4y8m33ea 179 7 hydrated hydrated JJ cord-021063-4y8m33ea 179 8 lipid lipid NN cord-021063-4y8m33ea 179 9 film film NN cord-021063-4y8m33ea 179 10 are be VBP cord-021063-4y8m33ea 179 11 repeatedly repeatedly RB cord-021063-4y8m33ea 179 12 passed pass VBN cord-021063-4y8m33ea 179 13 ( ( -LRB- cord-021063-4y8m33ea 179 14 extruded extrude VBN cord-021063-4y8m33ea 179 15 ) ) -RRB- cord-021063-4y8m33ea 179 16 through through IN cord-021063-4y8m33ea 179 17 a a DT cord-021063-4y8m33ea 179 18 filter filter NN cord-021063-4y8m33ea 179 19 under under IN cord-021063-4y8m33ea 179 20 pressure pressure NN cord-021063-4y8m33ea 179 21 . . . cord-021063-4y8m33ea 180 1 As as IN cord-021063-4y8m33ea 180 2 the the DT cord-021063-4y8m33ea 180 3 liposomes liposome NNS cord-021063-4y8m33ea 180 4 are be VBP cord-021063-4y8m33ea 180 5 forced force VBN cord-021063-4y8m33ea 180 6 through through IN cord-021063-4y8m33ea 180 7 the the DT cord-021063-4y8m33ea 180 8 pores pore NNS cord-021063-4y8m33ea 180 9 of of IN cord-021063-4y8m33ea 180 10 the the DT cord-021063-4y8m33ea 180 11 filter filter NN cord-021063-4y8m33ea 180 12 , , , cord-021063-4y8m33ea 180 13 they -PRON- PRP cord-021063-4y8m33ea 180 14 are be VBP cord-021063-4y8m33ea 180 15 converted convert VBN cord-021063-4y8m33ea 180 16 from from IN cord-021063-4y8m33ea 180 17 multilamellar multilamellar NNP cord-021063-4y8m33ea 180 18 to to IN cord-021063-4y8m33ea 180 19 unilamellar unilamellar NNP cord-021063-4y8m33ea 180 20 vesicles vesicle NNS cord-021063-4y8m33ea 180 21 , , , cord-021063-4y8m33ea 180 22 and and CC cord-021063-4y8m33ea 180 23 the the DT cord-021063-4y8m33ea 180 24 buffer buffer NN cord-021063-4y8m33ea 180 25 and and CC cord-021063-4y8m33ea 180 26 anything anything NN cord-021063-4y8m33ea 180 27 present present JJ cord-021063-4y8m33ea 180 28 in in IN cord-021063-4y8m33ea 180 29 it -PRON- PRP cord-021063-4y8m33ea 180 30 is be VBZ cord-021063-4y8m33ea 180 31 trapped trap VBN cord-021063-4y8m33ea 180 32 inside inside IN cord-021063-4y8m33ea 180 33 the the DT cord-021063-4y8m33ea 180 34 liposomes liposome NNS cord-021063-4y8m33ea 180 35 ( ( -LRB- cord-021063-4y8m33ea 180 36 Mayer Mayer NNP cord-021063-4y8m33ea 180 37 et et NNP cord-021063-4y8m33ea 180 38 al al NNP cord-021063-4y8m33ea 180 39 . . NNP cord-021063-4y8m33ea 180 40 , , , cord-021063-4y8m33ea 180 41 1986 1986 CD cord-021063-4y8m33ea 180 42 ) ) -RRB- cord-021063-4y8m33ea 180 43 . . . cord-021063-4y8m33ea 181 1 To to IN cord-021063-4y8m33ea 181 2 a a DT cord-021063-4y8m33ea 181 3 certain certain JJ cord-021063-4y8m33ea 181 4 extent extent NN cord-021063-4y8m33ea 181 5 , , , cord-021063-4y8m33ea 181 6 the the DT cord-021063-4y8m33ea 181 7 size size NN cord-021063-4y8m33ea 181 8 of of IN cord-021063-4y8m33ea 181 9 the the DT cord-021063-4y8m33ea 181 10 liposomes liposome NNS cord-021063-4y8m33ea 181 11 corresponds correspond VBZ cord-021063-4y8m33ea 181 12 to to IN cord-021063-4y8m33ea 181 13 the the DT cord-021063-4y8m33ea 181 14 pore pore NN cord-021063-4y8m33ea 181 15 size size NN cord-021063-4y8m33ea 181 16 of of IN cord-021063-4y8m33ea 181 17 the the DT cord-021063-4y8m33ea 181 18 filter filter NN cord-021063-4y8m33ea 181 19 used use VBN cord-021063-4y8m33ea 181 20 . . . cord-021063-4y8m33ea 182 1 Advantages advantage NNS cord-021063-4y8m33ea 182 2 of of IN cord-021063-4y8m33ea 182 3 this this DT cord-021063-4y8m33ea 182 4 technique technique NN cord-021063-4y8m33ea 182 5 are be VBP cord-021063-4y8m33ea 182 6 : : : cord-021063-4y8m33ea 182 7 ( ( -LRB- cord-021063-4y8m33ea 182 8 i i NN cord-021063-4y8m33ea 182 9 ) ) -RRB- cord-021063-4y8m33ea 182 10 nearly nearly RB cord-021063-4y8m33ea 182 11 any any DT cord-021063-4y8m33ea 182 12 lipid lipid NN cord-021063-4y8m33ea 182 13 or or CC cord-021063-4y8m33ea 182 14 lipid lipid NN cord-021063-4y8m33ea 182 15 mixture mixture NN cord-021063-4y8m33ea 182 16 can can MD cord-021063-4y8m33ea 182 17 be be VB cord-021063-4y8m33ea 182 18 used use VBN cord-021063-4y8m33ea 182 19 , , , cord-021063-4y8m33ea 182 20 ( ( -LRB- cord-021063-4y8m33ea 182 21 ii ii NN cord-021063-4y8m33ea 182 22 ) ) -RRB- cord-021063-4y8m33ea 182 23 liposome liposome NN cord-021063-4y8m33ea 182 24 size size NN cord-021063-4y8m33ea 182 25 from from IN cord-021063-4y8m33ea 182 26 25 25 CD cord-021063-4y8m33ea 182 27 to to TO cord-021063-4y8m33ea 182 28 100 100 CD cord-021063-4y8m33ea 182 29 nm nm NN cord-021063-4y8m33ea 182 30 in in IN cord-021063-4y8m33ea 182 31 diameter diameter NN cord-021063-4y8m33ea 182 32 can can MD cord-021063-4y8m33ea 182 33 be be VB cord-021063-4y8m33ea 182 34 controlled control VBN cord-021063-4y8m33ea 182 35 , , , cord-021063-4y8m33ea 182 36 and and CC cord-021063-4y8m33ea 182 37 ( ( -LRB- cord-021063-4y8m33ea 182 38 iii iii NN cord-021063-4y8m33ea 182 39 ) ) -RRB- cord-021063-4y8m33ea 183 1 the the DT cord-021063-4y8m33ea 183 2 encapsulation encapsulation NN cord-021063-4y8m33ea 183 3 efficiency efficiency NN cord-021063-4y8m33ea 183 4 is be VBZ cord-021063-4y8m33ea 183 5 excellent excellent JJ cord-021063-4y8m33ea 183 6 ( ( -LRB- cord-021063-4y8m33ea 183 7 up up IN cord-021063-4y8m33ea 183 8 to to TO cord-021063-4y8m33ea 183 9 30 30 CD cord-021063-4y8m33ea 183 10 % % NN cord-021063-4y8m33ea 183 11 ) ) -RRB- cord-021063-4y8m33ea 183 12 . . . cord-021063-4y8m33ea 184 1 The the DT cord-021063-4y8m33ea 184 2 main main JJ cord-021063-4y8m33ea 184 3 disadvantage disadvantage NN cord-021063-4y8m33ea 184 4 is be VBZ cord-021063-4y8m33ea 184 5 that that IN cord-021063-4y8m33ea 184 6 the the DT cord-021063-4y8m33ea 184 7 high high JJ cord-021063-4y8m33ea 184 8 pressures pressure NNS cord-021063-4y8m33ea 184 9 used use VBN cord-021063-4y8m33ea 184 10 in in IN cord-021063-4y8m33ea 184 11 the the DT cord-021063-4y8m33ea 184 12 extrusion extrusion NN cord-021063-4y8m33ea 184 13 process process NN cord-021063-4y8m33ea 184 14 can can MD cord-021063-4y8m33ea 184 15 fragment fragment VB cord-021063-4y8m33ea 184 16 the the DT cord-021063-4y8m33ea 184 17 DNA dna NN cord-021063-4y8m33ea 184 18 , , , cord-021063-4y8m33ea 184 19 and and CC cord-021063-4y8m33ea 184 20 denature denature VB cord-021063-4y8m33ea 184 21 or or CC cord-021063-4y8m33ea 184 22 dissociate dissociate VB cord-021063-4y8m33ea 184 23 DNA dna NN cord-021063-4y8m33ea 184 24 - - HYPH cord-021063-4y8m33ea 184 25 protein protein NN cord-021063-4y8m33ea 184 26 complexes complex NNS cord-021063-4y8m33ea 184 27 . . . cord-021063-4y8m33ea 185 1 A a DT cord-021063-4y8m33ea 185 2 central central JJ cord-021063-4y8m33ea 185 3 difficulty difficulty NN cord-021063-4y8m33ea 185 4 in in IN cord-021063-4y8m33ea 185 5 using use VBG cord-021063-4y8m33ea 185 6 liposomes liposome NNS cord-021063-4y8m33ea 185 7 for for IN cord-021063-4y8m33ea 185 8 gene gene NN cord-021063-4y8m33ea 185 9 therapy therapy NN cord-021063-4y8m33ea 185 10 is be VBZ cord-021063-4y8m33ea 185 11 the the DT cord-021063-4y8m33ea 185 12 entrapment entrapment NN cord-021063-4y8m33ea 185 13 of of IN cord-021063-4y8m33ea 185 14 the the DT cord-021063-4y8m33ea 185 15 DNA dna NN cord-021063-4y8m33ea 185 16 . . . cord-021063-4y8m33ea 186 1 The the DT cord-021063-4y8m33ea 186 2 ideal ideal JJ cord-021063-4y8m33ea 186 3 encapsulation encapsulation NN cord-021063-4y8m33ea 186 4 method method NN cord-021063-4y8m33ea 186 5 would would MD cord-021063-4y8m33ea 186 6 efficiently efficiently RB cord-021063-4y8m33ea 186 7 entrap entrap VB cord-021063-4y8m33ea 186 8 but but CC cord-021063-4y8m33ea 186 9 not not RB cord-021063-4y8m33ea 186 10 degrade degrade VB cord-021063-4y8m33ea 186 11 the the DT cord-021063-4y8m33ea 186 12 DNA dna NN cord-021063-4y8m33ea 186 13 . . . cord-021063-4y8m33ea 187 1 At at IN cord-021063-4y8m33ea 187 2 the the DT cord-021063-4y8m33ea 187 3 same same JJ cord-021063-4y8m33ea 187 4 time time NN cord-021063-4y8m33ea 187 5 , , , cord-021063-4y8m33ea 187 6 the the DT cord-021063-4y8m33ea 187 7 method method NN cord-021063-4y8m33ea 187 8 would would MD cord-021063-4y8m33ea 187 9 be be VB cord-021063-4y8m33ea 187 10 sufficiently sufficiently RB cord-021063-4y8m33ea 187 11 flexible flexible JJ cord-021063-4y8m33ea 187 12 with with IN cord-021063-4y8m33ea 187 13 regard regard NN cord-021063-4y8m33ea 187 14 to to IN cord-021063-4y8m33ea 187 15 size size NN cord-021063-4y8m33ea 187 16 and and CC cord-021063-4y8m33ea 187 17 vesicle vesicle NN cord-021063-4y8m33ea 187 18 composition composition NN cord-021063-4y8m33ea 187 19 to to TO cord-021063-4y8m33ea 187 20 allow allow VB cord-021063-4y8m33ea 187 21 targeting targeting NN cord-021063-4y8m33ea 187 22 of of IN cord-021063-4y8m33ea 187 23 liposomes liposome NNS cord-021063-4y8m33ea 187 24 based base VBN cord-021063-4y8m33ea 187 25 on on IN cord-021063-4y8m33ea 187 26 these these DT cord-021063-4y8m33ea 187 27 properties property NNS cord-021063-4y8m33ea 187 28 . . . cord-021063-4y8m33ea 188 1 DNA DNA NNP cord-021063-4y8m33ea 188 2 in in IN cord-021063-4y8m33ea 188 3 solution solution NN cord-021063-4y8m33ea 188 4 has have VBZ cord-021063-4y8m33ea 188 5 a a DT cord-021063-4y8m33ea 188 6 linear linear JJ cord-021063-4y8m33ea 188 7 conformation conformation NN cord-021063-4y8m33ea 188 8 . . . cord-021063-4y8m33ea 189 1 In in IN cord-021063-4y8m33ea 189 2 general general JJ cord-021063-4y8m33ea 189 3 , , , cord-021063-4y8m33ea 189 4 DNA dna NN cord-021063-4y8m33ea 189 5 restriction restriction NN cord-021063-4y8m33ea 189 6 fragments fragment NNS cord-021063-4y8m33ea 189 7 containing contain VBG cord-021063-4y8m33ea 189 8 an an DT cord-021063-4y8m33ea 189 9 entire entire JJ cord-021063-4y8m33ea 189 10 gene gene NN cord-021063-4y8m33ea 189 11 are be VBP cord-021063-4y8m33ea 189 12 much much RB cord-021063-4y8m33ea 189 13 longer long JJR cord-021063-4y8m33ea 189 14 than than IN cord-021063-4y8m33ea 189 15 the the DT cord-021063-4y8m33ea 189 16 diameter diameter NN cord-021063-4y8m33ea 189 17 of of IN cord-021063-4y8m33ea 189 18 com com NN cord-021063-4y8m33ea 189 19 - - HYPH cord-021063-4y8m33ea 189 20 monly monly NN cord-021063-4y8m33ea 189 21 used use VBN cord-021063-4y8m33ea 189 22 liposomes liposome NNS cord-021063-4y8m33ea 189 23 . . . cord-021063-4y8m33ea 190 1 It -PRON- PRP cord-021063-4y8m33ea 190 2 should should MD cord-021063-4y8m33ea 190 3 not not RB cord-021063-4y8m33ea 190 4 be be VB cord-021063-4y8m33ea 190 5 surprising surprising JJ cord-021063-4y8m33ea 190 6 then then RB cord-021063-4y8m33ea 190 7 that that IN cord-021063-4y8m33ea 190 8 most most JJS cord-021063-4y8m33ea 190 9 methods method NNS cord-021063-4y8m33ea 190 10 of of IN cord-021063-4y8m33ea 190 11 liposome liposome NN cord-021063-4y8m33ea 190 12 formation formation NN cord-021063-4y8m33ea 190 13 entrap entrap VBP cord-021063-4y8m33ea 190 14 DNA dna NN cord-021063-4y8m33ea 190 15 only only RB cord-021063-4y8m33ea 190 16 at at IN cord-021063-4y8m33ea 190 17 low low JJ cord-021063-4y8m33ea 190 18 efficiency efficiency NN cord-021063-4y8m33ea 190 19 , , , cord-021063-4y8m33ea 190 20 and and CC cord-021063-4y8m33ea 190 21 that that IN cord-021063-4y8m33ea 190 22 the the DT cord-021063-4y8m33ea 190 23 efficiency efficiency NN cord-021063-4y8m33ea 190 24 is be VBZ cord-021063-4y8m33ea 190 25 inversely inversely RB cord-021063-4y8m33ea 190 26 related relate VBN cord-021063-4y8m33ea 190 27 to to IN cord-021063-4y8m33ea 190 28 the the DT cord-021063-4y8m33ea 190 29 length length NN cord-021063-4y8m33ea 190 30 of of IN cord-021063-4y8m33ea 190 31 the the DT cord-021063-4y8m33ea 190 32 DNA dna NN cord-021063-4y8m33ea 190 33 ( ( -LRB- cord-021063-4y8m33ea 190 34 Fraley Fraley NNP cord-021063-4y8m33ea 190 35 et et NNP cord-021063-4y8m33ea 190 36 al al NNP cord-021063-4y8m33ea 190 37 . . NNP cord-021063-4y8m33ea 190 38 , , , cord-021063-4y8m33ea 190 39 1980 1980 CD cord-021063-4y8m33ea 190 40 ) ) -RRB- cord-021063-4y8m33ea 190 41 . . . cord-021063-4y8m33ea 191 1 Two two CD cord-021063-4y8m33ea 191 2 methods method NNS cord-021063-4y8m33ea 191 3 of of IN cord-021063-4y8m33ea 191 4 increasing increase VBG cord-021063-4y8m33ea 191 5 the the DT cord-021063-4y8m33ea 191 6 entrapment entrapment NN cord-021063-4y8m33ea 191 7 efficiency efficiency NN cord-021063-4y8m33ea 191 8 of of IN cord-021063-4y8m33ea 191 9 DNA DNA NNP cord-021063-4y8m33ea 191 10 have have VBP cord-021063-4y8m33ea 191 11 been be VBN cord-021063-4y8m33ea 191 12 developed develop VBN cord-021063-4y8m33ea 191 13 . . . cord-021063-4y8m33ea 192 1 In in IN cord-021063-4y8m33ea 192 2 the the DT cord-021063-4y8m33ea 192 3 first first JJ cord-021063-4y8m33ea 192 4 , , , cord-021063-4y8m33ea 192 5 the the DT cord-021063-4y8m33ea 192 6 liposomes liposome NNS cord-021063-4y8m33ea 192 7 are be VBP cord-021063-4y8m33ea 192 8 formed form VBN cord-021063-4y8m33ea 192 9 in in IN cord-021063-4y8m33ea 192 10 such such PDT cord-021063-4y8m33ea 192 11 a a DT cord-021063-4y8m33ea 192 12 way way NN cord-021063-4y8m33ea 192 13 that that WDT cord-021063-4y8m33ea 192 14 the the DT cord-021063-4y8m33ea 192 15 aqueous aqueous JJ cord-021063-4y8m33ea 192 16 phase phase NN cord-021063-4y8m33ea 192 17 , , , cord-021063-4y8m33ea 192 18 containing contain VBG cord-021063-4y8m33ea 192 19 the the DT cord-021063-4y8m33ea 192 20 DNA dna NN cord-021063-4y8m33ea 192 21 , , , cord-021063-4y8m33ea 192 22 is be VBZ cord-021063-4y8m33ea 192 23 broken break VBN cord-021063-4y8m33ea 192 24 into into IN cord-021063-4y8m33ea 192 25 droplets droplet NNS cord-021063-4y8m33ea 192 26 small small JJ cord-021063-4y8m33ea 192 27 enough enough RB cord-021063-4y8m33ea 192 28 such such JJ cord-021063-4y8m33ea 192 29 that that IN cord-021063-4y8m33ea 192 30 the the DT cord-021063-4y8m33ea 192 31 DNA dna NN cord-021063-4y8m33ea 192 32 is be VBZ cord-021063-4y8m33ea 192 33 forced force VBN cord-021063-4y8m33ea 192 34 to to TO cord-021063-4y8m33ea 192 35 curl curl VB cord-021063-4y8m33ea 192 36 in in RP cord-021063-4y8m33ea 192 37 upon upon IN cord-021063-4y8m33ea 192 38 itself -PRON- PRP cord-021063-4y8m33ea 192 39 to to TO cord-021063-4y8m33ea 192 40 remain remain VB cord-021063-4y8m33ea 192 41 within within IN cord-021063-4y8m33ea 192 42 the the DT cord-021063-4y8m33ea 192 43 droplet droplet NN cord-021063-4y8m33ea 192 44 . . . cord-021063-4y8m33ea 193 1 This this DT cord-021063-4y8m33ea 193 2 probably probably RB cord-021063-4y8m33ea 193 3 occurs occur VBZ cord-021063-4y8m33ea 193 4 during during IN cord-021063-4y8m33ea 193 5 REV REV NNP cord-021063-4y8m33ea 193 6 formation formation NN cord-021063-4y8m33ea 193 7 . . . cord-021063-4y8m33ea 194 1 The the DT cord-021063-4y8m33ea 194 2 other other JJ cord-021063-4y8m33ea 194 3 method method NN cord-021063-4y8m33ea 194 4 achieves achieve VBZ cord-021063-4y8m33ea 194 5 the the DT cord-021063-4y8m33ea 194 6 same same JJ cord-021063-4y8m33ea 194 7 result result NN cord-021063-4y8m33ea 194 8 by by IN cord-021063-4y8m33ea 194 9 complexing complexe VBG cord-021063-4y8m33ea 194 10 the the DT cord-021063-4y8m33ea 194 11 DNA dna NN cord-021063-4y8m33ea 194 12 with with IN cord-021063-4y8m33ea 194 13 some some DT cord-021063-4y8m33ea 194 14 substance substance NN cord-021063-4y8m33ea 194 15 in in IN cord-021063-4y8m33ea 194 16 a a DT cord-021063-4y8m33ea 194 17 tight tight JJ cord-021063-4y8m33ea 194 18 and and CC cord-021063-4y8m33ea 194 19 compact compact JJ cord-021063-4y8m33ea 194 20 aggregate aggregate NN cord-021063-4y8m33ea 194 21 . . . cord-021063-4y8m33ea 195 1 To to IN cord-021063-4y8m33ea 195 2 date date NN cord-021063-4y8m33ea 195 3 , , , cord-021063-4y8m33ea 195 4 this this DT cord-021063-4y8m33ea 195 5 has have VBZ cord-021063-4y8m33ea 195 6 been be VBN cord-021063-4y8m33ea 195 7 done do VBN cord-021063-4y8m33ea 195 8 with with IN cord-021063-4y8m33ea 195 9 spermine spermine FW cord-021063-4y8m33ea 195 10 ( ( -LRB- cord-021063-4y8m33ea 195 11 Tikchonenko Tikchonenko NNP cord-021063-4y8m33ea 195 12 et et FW cord-021063-4y8m33ea 195 13 al al NNP cord-021063-4y8m33ea 195 14 . . NNP cord-021063-4y8m33ea 195 15 , , , cord-021063-4y8m33ea 195 16 1988 1988 CD cord-021063-4y8m33ea 195 17 ) ) -RRB- cord-021063-4y8m33ea 195 18 and and CC cord-021063-4y8m33ea 195 19 basic basic JJ cord-021063-4y8m33ea 195 20 proteins protein NNS cord-021063-4y8m33ea 195 21 ( ( -LRB- cord-021063-4y8m33ea 195 22 Jay Jay NNP cord-021063-4y8m33ea 195 23 and and CC cord-021063-4y8m33ea 195 24 Gilbert Gilbert NNP cord-021063-4y8m33ea 195 25 , , , cord-021063-4y8m33ea 195 26 1987 1987 CD cord-021063-4y8m33ea 195 27 ) ) -RRB- cord-021063-4y8m33ea 195 28 . . . cord-021063-4y8m33ea 196 1 The the DT cord-021063-4y8m33ea 196 2 efficiency efficiency NN cord-021063-4y8m33ea 196 3 of of IN cord-021063-4y8m33ea 196 4 encapsulation encapsulation NN cord-021063-4y8m33ea 196 5 can can MD cord-021063-4y8m33ea 196 6 also also RB cord-021063-4y8m33ea 196 7 be be VB cord-021063-4y8m33ea 196 8 increased increase VBN cord-021063-4y8m33ea 196 9 by by IN cord-021063-4y8m33ea 196 10 compacting compact VBG cord-021063-4y8m33ea 196 11 the the DT cord-021063-4y8m33ea 196 12 DNA dna NN cord-021063-4y8m33ea 196 13 in in IN cord-021063-4y8m33ea 196 14 phage phage NN cord-021063-4y8m33ea 196 15 head head NN cord-021063-4y8m33ea 196 16 particles particle NNS cord-021063-4y8m33ea 196 17 ( ( -LRB- cord-021063-4y8m33ea 196 18 Szelei Szelei NNP cord-021063-4y8m33ea 196 19 and and CC cord-021063-4y8m33ea 196 20 Duda Duda NNP cord-021063-4y8m33ea 196 21 , , , cord-021063-4y8m33ea 196 22 1989 1989 CD cord-021063-4y8m33ea 196 23 ) ) -RRB- cord-021063-4y8m33ea 196 24 before before IN cord-021063-4y8m33ea 196 25 liposomal liposomal JJ cord-021063-4y8m33ea 196 26 entrapment entrapment NN cord-021063-4y8m33ea 196 27 . . . cord-021063-4y8m33ea 197 1 The the DT cord-021063-4y8m33ea 197 2 basis basis NN cord-021063-4y8m33ea 197 3 for for IN cord-021063-4y8m33ea 197 4 successful successful JJ cord-021063-4y8m33ea 197 5 transfections transfection NNS cord-021063-4y8m33ea 197 6 by by IN cord-021063-4y8m33ea 197 7 liposomal liposomal NN cord-021063-4y8m33ea 197 8 vectors vector NNS cord-021063-4y8m33ea 197 9 delivered deliver VBD cord-021063-4y8m33ea 197 10 intravenously intravenously RB cord-021063-4y8m33ea 197 11 lies lie VBZ cord-021063-4y8m33ea 197 12 in in IN cord-021063-4y8m33ea 197 13 the the DT cord-021063-4y8m33ea 197 14 maximization maximization NN cord-021063-4y8m33ea 197 15 of of IN cord-021063-4y8m33ea 197 16 the the DT cord-021063-4y8m33ea 197 17 in in IN cord-021063-4y8m33ea 197 18 vivo vivo NNP cord-021063-4y8m33ea 197 19 circulation circulation NN cord-021063-4y8m33ea 197 20 time time NN cord-021063-4y8m33ea 197 21 of of IN cord-021063-4y8m33ea 197 22 the the DT cord-021063-4y8m33ea 197 23 liposomes liposome NNS cord-021063-4y8m33ea 197 24 . . . cord-021063-4y8m33ea 198 1 Most Most JJS cord-021063-4y8m33ea 198 2 liposome liposome NN cord-021063-4y8m33ea 198 3 formulations formulation NNS cord-021063-4y8m33ea 198 4 are be VBP cord-021063-4y8m33ea 198 5 cleared clear VBN cord-021063-4y8m33ea 198 6 rapidly rapidly RB cord-021063-4y8m33ea 198 7 from from IN cord-021063-4y8m33ea 198 8 the the DT cord-021063-4y8m33ea 198 9 circulation circulation NN cord-021063-4y8m33ea 198 10 by by IN cord-021063-4y8m33ea 198 11 the the DT cord-021063-4y8m33ea 198 12 reticuloendothelial reticuloendothelial JJ cord-021063-4y8m33ea 198 13 system system NN cord-021063-4y8m33ea 198 14 ( ( -LRB- cord-021063-4y8m33ea 198 15 RES RES NNP cord-021063-4y8m33ea 198 16 ) ) -RRB- cord-021063-4y8m33ea 198 17 , , , cord-021063-4y8m33ea 198 18 with with IN cord-021063-4y8m33ea 198 19 large large JJ cord-021063-4y8m33ea 198 20 amounts amount NNS cord-021063-4y8m33ea 198 21 accumulating accumulate VBG cord-021063-4y8m33ea 198 22 in in IN cord-021063-4y8m33ea 198 23 macrophages macrophage NNS cord-021063-4y8m33ea 198 24 ( ( -LRB- cord-021063-4y8m33ea 198 25 Allen Allen NNP cord-021063-4y8m33ea 198 26 et et NNP cord-021063-4y8m33ea 198 27 al al NNP cord-021063-4y8m33ea 198 28 . . NNP cord-021063-4y8m33ea 198 29 , , , cord-021063-4y8m33ea 198 30 1989 1989 CD cord-021063-4y8m33ea 198 31 ) ) -RRB- cord-021063-4y8m33ea 198 32 . . . cord-021063-4y8m33ea 199 1 If if IN cord-021063-4y8m33ea 199 2 the the DT cord-021063-4y8m33ea 199 3 intended intend VBN cord-021063-4y8m33ea 199 4 target target NN cord-021063-4y8m33ea 199 5 of of IN cord-021063-4y8m33ea 199 6 the the DT cord-021063-4y8m33ea 199 7 gene gene NN cord-021063-4y8m33ea 199 8 therapy therapy NN cord-021063-4y8m33ea 199 9 is be VBZ cord-021063-4y8m33ea 199 10 the the DT cord-021063-4y8m33ea 199 11 RES RES NNP cord-021063-4y8m33ea 199 12 , , , cord-021063-4y8m33ea 199 13 as as IN cord-021063-4y8m33ea 199 14 in in IN cord-021063-4y8m33ea 199 15 Gaucher Gaucher NNP cord-021063-4y8m33ea 199 16 's 's POS cord-021063-4y8m33ea 199 17 disease disease NN cord-021063-4y8m33ea 199 18 , , , cord-021063-4y8m33ea 199 19 this this DT cord-021063-4y8m33ea 199 20 is be VBZ cord-021063-4y8m33ea 199 21 a a DT cord-021063-4y8m33ea 199 22 benefit benefit NN cord-021063-4y8m33ea 199 23 . . . cord-021063-4y8m33ea 200 1 In in IN cord-021063-4y8m33ea 200 2 most most JJS cord-021063-4y8m33ea 200 3 cases case NNS cord-021063-4y8m33ea 200 4 , , , cord-021063-4y8m33ea 200 5 however however RB cord-021063-4y8m33ea 200 6 , , , cord-021063-4y8m33ea 200 7 this this DT cord-021063-4y8m33ea 200 8 fate fate NN cord-021063-4y8m33ea 200 9 will will MD cord-021063-4y8m33ea 200 10 only only RB cord-021063-4y8m33ea 200 11 serve serve VB cord-021063-4y8m33ea 200 12 to to TO cord-021063-4y8m33ea 200 13 reduce reduce VB cord-021063-4y8m33ea 200 14 the the DT cord-021063-4y8m33ea 200 15 number number NN cord-021063-4y8m33ea 200 16 of of IN cord-021063-4y8m33ea 200 17 liposomes liposome NNS cord-021063-4y8m33ea 200 18 being be VBG cord-021063-4y8m33ea 200 19 exposed expose VBN cord-021063-4y8m33ea 200 20 to to IN cord-021063-4y8m33ea 200 21 their -PRON- PRP$ cord-021063-4y8m33ea 200 22 intended intend VBN cord-021063-4y8m33ea 200 23 target target NN cord-021063-4y8m33ea 200 24 cell cell NN cord-021063-4y8m33ea 200 25 population population NN cord-021063-4y8m33ea 200 26 . . . cord-021063-4y8m33ea 201 1 While while IN cord-021063-4y8m33ea 201 2 several several JJ cord-021063-4y8m33ea 201 3 different different JJ cord-021063-4y8m33ea 201 4 strategies strategy NNS cord-021063-4y8m33ea 201 5 have have VBP cord-021063-4y8m33ea 201 6 been be VBN cord-021063-4y8m33ea 201 7 explored explore VBN cord-021063-4y8m33ea 201 8 to to TO cord-021063-4y8m33ea 201 9 lengthen lengthen VB cord-021063-4y8m33ea 201 10 the the DT cord-021063-4y8m33ea 201 11 circulation circulation NN cord-021063-4y8m33ea 201 12 half half JJ cord-021063-4y8m33ea 201 13 - - HYPH cord-021063-4y8m33ea 201 14 life life NN cord-021063-4y8m33ea 201 15 of of IN cord-021063-4y8m33ea 201 16 liposomes liposome NNS cord-021063-4y8m33ea 201 17 , , , cord-021063-4y8m33ea 201 18 they -PRON- PRP cord-021063-4y8m33ea 201 19 all all DT cord-021063-4y8m33ea 201 20 have have VBP cord-021063-4y8m33ea 201 21 certain certain JJ cord-021063-4y8m33ea 201 22 aspects aspect NNS cord-021063-4y8m33ea 201 23 in in IN cord-021063-4y8m33ea 201 24 common common JJ cord-021063-4y8m33ea 202 1 ( ( -LRB- cord-021063-4y8m33ea 202 2 Allen Allen NNP cord-021063-4y8m33ea 202 3 et et NNP cord-021063-4y8m33ea 202 4 al al NNP cord-021063-4y8m33ea 202 5 . . . cord-021063-4y8m33ea 203 1 , , , cord-021063-4y8m33ea 203 2 1989 1989 CD cord-021063-4y8m33ea 203 3 ; ; : cord-021063-4y8m33ea 203 4 Gabizon Gabizon NNP cord-021063-4y8m33ea 203 5 and and CC cord-021063-4y8m33ea 203 6 Papahadjopoulos Papahadjopoulos NNP cord-021063-4y8m33ea 203 7 , , , cord-021063-4y8m33ea 203 8 1992 1992 CD cord-021063-4y8m33ea 203 9 ) ) -RRB- cord-021063-4y8m33ea 203 10 . . . cord-021063-4y8m33ea 204 1 First first RB cord-021063-4y8m33ea 204 2 , , , cord-021063-4y8m33ea 204 3 they -PRON- PRP cord-021063-4y8m33ea 204 4 seek seek VBP cord-021063-4y8m33ea 204 5 to to TO cord-021063-4y8m33ea 204 6 make make VB cord-021063-4y8m33ea 204 7 the the DT cord-021063-4y8m33ea 204 8 liposomes liposome NNS cord-021063-4y8m33ea 204 9 as as RB cord-021063-4y8m33ea 204 10 small small JJ cord-021063-4y8m33ea 204 11 as as IN cord-021063-4y8m33ea 204 12 possible possible JJ cord-021063-4y8m33ea 204 13 . . . cord-021063-4y8m33ea 205 1 This this DT cord-021063-4y8m33ea 205 2 seems seem VBZ cord-021063-4y8m33ea 205 3 to to TO cord-021063-4y8m33ea 205 4 reduce reduce VB cord-021063-4y8m33ea 205 5 their -PRON- PRP$ cord-021063-4y8m33ea 205 6 interaction interaction NN cord-021063-4y8m33ea 205 7 with with IN cord-021063-4y8m33ea 205 8 the the DT cord-021063-4y8m33ea 205 9 RES res NN cord-021063-4y8m33ea 205 10 . . . cord-021063-4y8m33ea 206 1 Second second RB cord-021063-4y8m33ea 206 2 , , , cord-021063-4y8m33ea 206 3 they -PRON- PRP cord-021063-4y8m33ea 206 4 are be VBP cord-021063-4y8m33ea 206 5 designed design VBN cord-021063-4y8m33ea 206 6 to to TO cord-021063-4y8m33ea 206 7 make make VB cord-021063-4y8m33ea 206 8 the the DT cord-021063-4y8m33ea 206 9 liposomal liposomal JJ cord-021063-4y8m33ea 206 10 surface surface NN cord-021063-4y8m33ea 206 11 as as RB cord-021063-4y8m33ea 206 12 much much RB cord-021063-4y8m33ea 206 13 like like IN cord-021063-4y8m33ea 206 14 the the DT cord-021063-4y8m33ea 206 15 surface surface NN cord-021063-4y8m33ea 206 16 of of IN cord-021063-4y8m33ea 206 17 a a DT cord-021063-4y8m33ea 206 18 normal normal JJ cord-021063-4y8m33ea 206 19 cell cell NN cord-021063-4y8m33ea 206 20 as as IN cord-021063-4y8m33ea 206 21 possible possible JJ cord-021063-4y8m33ea 206 22 . . . cord-021063-4y8m33ea 207 1 This this DT cord-021063-4y8m33ea 207 2 can can MD cord-021063-4y8m33ea 207 3 be be VB cord-021063-4y8m33ea 207 4 accomplished accomplish VBN cord-021063-4y8m33ea 207 5 by by IN cord-021063-4y8m33ea 207 6 using use VBG cord-021063-4y8m33ea 207 7 lipid lipid NN cord-021063-4y8m33ea 207 8 formulations formulation NNS cord-021063-4y8m33ea 207 9 containing contain VBG cord-021063-4y8m33ea 207 10 a a DT cord-021063-4y8m33ea 207 11 high high JJ cord-021063-4y8m33ea 207 12 fraction fraction NN cord-021063-4y8m33ea 207 13 of of IN cord-021063-4y8m33ea 207 14 cholesterol cholesterol NN cord-021063-4y8m33ea 207 15 , , , cord-021063-4y8m33ea 207 16 high high JJ cord-021063-4y8m33ea 207 17 transition transition NN cord-021063-4y8m33ea 207 18 temperature temperature NN cord-021063-4y8m33ea 207 19 phospholipids phospholipid NNS cord-021063-4y8m33ea 207 20 , , , cord-021063-4y8m33ea 207 21 and and CC cord-021063-4y8m33ea 207 22 a a DT cord-021063-4y8m33ea 207 23 substantial substantial JJ cord-021063-4y8m33ea 207 24 fraction fraction NN cord-021063-4y8m33ea 207 25 of of IN cord-021063-4y8m33ea 207 26 sphingomyelin sphingomyelin NN cord-021063-4y8m33ea 207 27 or or CC cord-021063-4y8m33ea 207 28 the the DT cord-021063-4y8m33ea 207 29 ganglioside ganglioside NN cord-021063-4y8m33ea 207 30 GM GM NNP cord-021063-4y8m33ea 207 31 1 1 CD cord-021063-4y8m33ea 207 32 . . . cord-021063-4y8m33ea 208 1 A a DT cord-021063-4y8m33ea 208 2 different different JJ cord-021063-4y8m33ea 208 3 approach approach NN cord-021063-4y8m33ea 208 4 has have VBZ cord-021063-4y8m33ea 208 5 been be VBN cord-021063-4y8m33ea 208 6 to to TO cord-021063-4y8m33ea 208 7 modify modify VB cord-021063-4y8m33ea 208 8 the the DT cord-021063-4y8m33ea 208 9 liposomal liposomal JJ cord-021063-4y8m33ea 208 10 phospholipids phospholipid NNS cord-021063-4y8m33ea 208 11 by by IN cord-021063-4y8m33ea 208 12 addition addition NN cord-021063-4y8m33ea 208 13 of of IN cord-021063-4y8m33ea 208 14 polyethylene polyethylene NN cord-021063-4y8m33ea 208 15 glycol glycol NN cord-021063-4y8m33ea 208 16 ( ( -LRB- cord-021063-4y8m33ea 208 17 PEG PEG NNP cord-021063-4y8m33ea 208 18 ) ) -RRB- cord-021063-4y8m33ea 208 19 to to IN cord-021063-4y8m33ea 208 20 the the DT cord-021063-4y8m33ea 208 21 polar polar JJ cord-021063-4y8m33ea 208 22 headgroup headgroup NN cord-021063-4y8m33ea 208 23 ( ( -LRB- cord-021063-4y8m33ea 208 24 Lasic Lasic NNP cord-021063-4y8m33ea 208 25 et et FW cord-021063-4y8m33ea 208 26 al al NNP cord-021063-4y8m33ea 208 27 . . NNP cord-021063-4y8m33ea 208 28 , , , cord-021063-4y8m33ea 208 29 1991 1991 CD cord-021063-4y8m33ea 208 30 ; ; : cord-021063-4y8m33ea 208 31 Blume Blume NNP cord-021063-4y8m33ea 208 32 and and CC cord-021063-4y8m33ea 208 33 Cevc Cevc NNP cord-021063-4y8m33ea 208 34 , , , cord-021063-4y8m33ea 208 35 1993 1993 CD cord-021063-4y8m33ea 208 36 ) ) -RRB- cord-021063-4y8m33ea 208 37 . . . cord-021063-4y8m33ea 209 1 PEG peg NN cord-021063-4y8m33ea 209 2 - - HYPH cord-021063-4y8m33ea 209 3 modified modify VBN cord-021063-4y8m33ea 209 4 lipids lipid NNS cord-021063-4y8m33ea 209 5 have have VBP cord-021063-4y8m33ea 209 6 a a DT cord-021063-4y8m33ea 209 7 higher high JJR cord-021063-4y8m33ea 209 8 hydrophilicity hydrophilicity NN cord-021063-4y8m33ea 209 9 than than IN cord-021063-4y8m33ea 209 10 native native JJ cord-021063-4y8m33ea 209 11 lipids lipid NNS cord-021063-4y8m33ea 209 12 , , , cord-021063-4y8m33ea 209 13 and and CC cord-021063-4y8m33ea 209 14 appear appear VBP cord-021063-4y8m33ea 209 15 to to TO cord-021063-4y8m33ea 209 16 escape escape VB cord-021063-4y8m33ea 209 17 recognition recognition NN cord-021063-4y8m33ea 209 18 by by IN cord-021063-4y8m33ea 209 19 macrophages macrophage NNS cord-021063-4y8m33ea 209 20 . . . cord-021063-4y8m33ea 210 1 A a DT cord-021063-4y8m33ea 210 2 potential potential JJ cord-021063-4y8m33ea 210 3 disadvantage disadvantage NN cord-021063-4y8m33ea 210 4 of of IN cord-021063-4y8m33ea 210 5 this this DT cord-021063-4y8m33ea 210 6 approach approach NN cord-021063-4y8m33ea 210 7 is be VBZ cord-021063-4y8m33ea 210 8 that that IN cord-021063-4y8m33ea 210 9 targeting targeting NN cord-021063-4y8m33ea 210 10 of of IN cord-021063-4y8m33ea 210 11 liposomes liposome NNS cord-021063-4y8m33ea 210 12 with with IN cord-021063-4y8m33ea 210 13 covalently covalently RB cord-021063-4y8m33ea 210 14 attached attach VBN cord-021063-4y8m33ea 210 15 antibodies antibody NNS cord-021063-4y8m33ea 210 16 ( ( -LRB- cord-021063-4y8m33ea 210 17 see see VB cord-021063-4y8m33ea 210 18 below below RB cord-021063-4y8m33ea 210 19 ) ) -RRB- cord-021063-4y8m33ea 210 20 is be VBZ cord-021063-4y8m33ea 210 21 inhibited inhibit VBN cord-021063-4y8m33ea 210 22 by by IN cord-021063-4y8m33ea 210 23 the the DT cord-021063-4y8m33ea 210 24 presence presence NN cord-021063-4y8m33ea 210 25 of of IN cord-021063-4y8m33ea 210 26 PEG peg NN cord-021063-4y8m33ea 210 27 - - HYPH cord-021063-4y8m33ea 210 28 modified modify VBN cord-021063-4y8m33ea 210 29 lipids lipid NNS cord-021063-4y8m33ea 211 1 ( ( -LRB- cord-021063-4y8m33ea 211 2 Klibanov Klibanov NNP cord-021063-4y8m33ea 211 3 et et NNP cord-021063-4y8m33ea 211 4 al al NNP cord-021063-4y8m33ea 211 5 . . NNP cord-021063-4y8m33ea 211 6 , , , cord-021063-4y8m33ea 211 7 1991 1991 CD cord-021063-4y8m33ea 211 8 ) ) -RRB- cord-021063-4y8m33ea 211 9 . . . cord-021063-4y8m33ea 212 1 Once once RB cord-021063-4y8m33ea 212 2 a a DT cord-021063-4y8m33ea 212 3 liposome liposome NN cord-021063-4y8m33ea 212 4 formulation formulation NN cord-021063-4y8m33ea 212 5 has have VBZ cord-021063-4y8m33ea 212 6 been be VBN cord-021063-4y8m33ea 212 7 settled settle VBN cord-021063-4y8m33ea 212 8 upon upon IN cord-021063-4y8m33ea 212 9 , , , cord-021063-4y8m33ea 212 10 attention attention NN cord-021063-4y8m33ea 212 11 must must MD cord-021063-4y8m33ea 212 12 be be VB cord-021063-4y8m33ea 212 13 paid pay VBN cord-021063-4y8m33ea 212 14 to to IN cord-021063-4y8m33ea 212 15 limiting limit VBG cord-021063-4y8m33ea 212 16 the the DT cord-021063-4y8m33ea 212 17 number number NN cord-021063-4y8m33ea 212 18 of of IN cord-021063-4y8m33ea 212 19 cells cell NNS cord-021063-4y8m33ea 212 20 exposed expose VBN cord-021063-4y8m33ea 212 21 to to IN cord-021063-4y8m33ea 212 22 the the DT cord-021063-4y8m33ea 212 23 DNA dna NN cord-021063-4y8m33ea 212 24 delivered deliver VBN cord-021063-4y8m33ea 212 25 by by IN cord-021063-4y8m33ea 212 26 the the DT cord-021063-4y8m33ea 212 27 liposomes liposome NNS cord-021063-4y8m33ea 212 28 . . . cord-021063-4y8m33ea 213 1 This this DT cord-021063-4y8m33ea 213 2 is be VBZ cord-021063-4y8m33ea 213 3 necessary necessary JJ cord-021063-4y8m33ea 213 4 for for IN cord-021063-4y8m33ea 213 5 several several JJ cord-021063-4y8m33ea 213 6 reasons reason NNS cord-021063-4y8m33ea 213 7 . . . cord-021063-4y8m33ea 214 1 First first RB cord-021063-4y8m33ea 214 2 , , , cord-021063-4y8m33ea 214 3 if if IN cord-021063-4y8m33ea 214 4 the the DT cord-021063-4y8m33ea 214 5 DNA dna NN cord-021063-4y8m33ea 214 6 will will MD cord-021063-4y8m33ea 214 7 be be VB cord-021063-4y8m33ea 214 8 integrated integrate VBN cord-021063-4y8m33ea 214 9 into into IN cord-021063-4y8m33ea 214 10 the the DT cord-021063-4y8m33ea 214 11 host host NN cord-021063-4y8m33ea 214 12 cell cell NN cord-021063-4y8m33ea 214 13 's 's POS cord-021063-4y8m33ea 214 14 genome genome NN cord-021063-4y8m33ea 214 15 , , , cord-021063-4y8m33ea 214 16 there there EX cord-021063-4y8m33ea 214 17 is be VBZ cord-021063-4y8m33ea 214 18 a a DT cord-021063-4y8m33ea 214 19 chance chance NN cord-021063-4y8m33ea 214 20 that that IN cord-021063-4y8m33ea 214 21 insertional insertional JJ cord-021063-4y8m33ea 214 22 mutagenesis mutagenesis NN cord-021063-4y8m33ea 214 23 will will MD cord-021063-4y8m33ea 214 24 lead lead VB cord-021063-4y8m33ea 214 25 to to IN cord-021063-4y8m33ea 214 26 activation activation NN cord-021063-4y8m33ea 214 27 of of IN cord-021063-4y8m33ea 214 28 a a DT cord-021063-4y8m33ea 214 29 proto proto JJ cord-021063-4y8m33ea 214 30 - - HYPH cord-021063-4y8m33ea 214 31 oncogene oncogene NN cord-021063-4y8m33ea 214 32 and and CC cord-021063-4y8m33ea 214 33 the the DT cord-021063-4y8m33ea 214 34 development development NN cord-021063-4y8m33ea 214 35 of of IN cord-021063-4y8m33ea 214 36 cancer cancer NN cord-021063-4y8m33ea 214 37 by by IN cord-021063-4y8m33ea 214 38 the the DT cord-021063-4y8m33ea 214 39 host host NN cord-021063-4y8m33ea 214 40 . . . cord-021063-4y8m33ea 215 1 By by IN cord-021063-4y8m33ea 215 2 limiting limit VBG cord-021063-4y8m33ea 215 3 the the DT cord-021063-4y8m33ea 215 4 sites site NNS cord-021063-4y8m33ea 215 5 of of IN cord-021063-4y8m33ea 215 6 DNA dna NN cord-021063-4y8m33ea 215 7 delivery delivery NN cord-021063-4y8m33ea 215 8 , , , cord-021063-4y8m33ea 215 9 the the DT cord-021063-4y8m33ea 215 10 chance chance NN cord-021063-4y8m33ea 215 11 of of IN cord-021063-4y8m33ea 215 12 insertional insertional JJ cord-021063-4y8m33ea 215 13 mutagenesis mutagenesis NN cord-021063-4y8m33ea 215 14 is be VBZ cord-021063-4y8m33ea 215 15 lowered lower VBN cord-021063-4y8m33ea 215 16 . . . cord-021063-4y8m33ea 216 1 Second second RB cord-021063-4y8m33ea 216 2 , , , cord-021063-4y8m33ea 216 3 limiting limit VBG cord-021063-4y8m33ea 216 4 the the DT cord-021063-4y8m33ea 216 5 number number NN cord-021063-4y8m33ea 216 6 of of IN cord-021063-4y8m33ea 216 7 cells cell NNS cord-021063-4y8m33ea 216 8 that that WDT cord-021063-4y8m33ea 216 9 are be VBP cord-021063-4y8m33ea 216 10 transfected transfecte VBN cord-021063-4y8m33ea 216 11 reduces reduce VBZ cord-021063-4y8m33ea 216 12 the the DT cord-021063-4y8m33ea 216 13 amount amount NN cord-021063-4y8m33ea 216 14 of of IN cord-021063-4y8m33ea 216 15 DNA dna NN cord-021063-4y8m33ea 216 16 , , , cord-021063-4y8m33ea 216 17 lipid lipid NN cord-021063-4y8m33ea 216 18 , , , cord-021063-4y8m33ea 216 19 and and CC cord-021063-4y8m33ea 216 20 other other JJ cord-021063-4y8m33ea 216 21 proteins protein NNS cord-021063-4y8m33ea 216 22 needed need VBN cord-021063-4y8m33ea 216 23 to to TO cord-021063-4y8m33ea 216 24 perform perform VB cord-021063-4y8m33ea 216 25 the the DT cord-021063-4y8m33ea 216 26 gene gene NN cord-021063-4y8m33ea 216 27 therapy therapy NN cord-021063-4y8m33ea 216 28 . . . cord-021063-4y8m33ea 217 1 This this DT cord-021063-4y8m33ea 217 2 reduction reduction NN cord-021063-4y8m33ea 217 3 can can MD cord-021063-4y8m33ea 217 4 be be VB cord-021063-4y8m33ea 217 5 substantial substantial JJ cord-021063-4y8m33ea 217 6 , , , cord-021063-4y8m33ea 217 7 and and CC cord-021063-4y8m33ea 217 8 can can MD cord-021063-4y8m33ea 217 9 reduce reduce VB cord-021063-4y8m33ea 217 10 potential potential JJ cord-021063-4y8m33ea 217 11 systemic systemic JJ cord-021063-4y8m33ea 217 12 toxicities toxicity NNS cord-021063-4y8m33ea 217 13 , , , cord-021063-4y8m33ea 217 14 as as RB cord-021063-4y8m33ea 217 15 well well RB cord-021063-4y8m33ea 217 16 as as IN cord-021063-4y8m33ea 217 17 cost cost NN cord-021063-4y8m33ea 217 18 . . . cord-021063-4y8m33ea 218 1 Table table NN cord-021063-4y8m33ea 218 2 4 4 CD cord-021063-4y8m33ea 218 3 compares compare VBZ cord-021063-4y8m33ea 218 4 some some DT cord-021063-4y8m33ea 218 5 different different JJ cord-021063-4y8m33ea 218 6 methods method NNS cord-021063-4y8m33ea 218 7 of of IN cord-021063-4y8m33ea 218 8 targeting target VBG cord-021063-4y8m33ea 218 9 liposomes liposome NNS cord-021063-4y8m33ea 218 10 to to IN cord-021063-4y8m33ea 218 11 specific specific JJ cord-021063-4y8m33ea 218 12 cell cell NN cord-021063-4y8m33ea 218 13 types type NNS cord-021063-4y8m33ea 218 14 . . . cord-021063-4y8m33ea 219 1 There there EX cord-021063-4y8m33ea 219 2 are be VBP cord-021063-4y8m33ea 219 3 three three CD cord-021063-4y8m33ea 219 4 general general JJ cord-021063-4y8m33ea 219 5 methods method NNS cord-021063-4y8m33ea 219 6 by by IN cord-021063-4y8m33ea 219 7 which which WDT cord-021063-4y8m33ea 219 8 liposomes liposome NNS cord-021063-4y8m33ea 219 9 may may MD cord-021063-4y8m33ea 219 10 be be VB cord-021063-4y8m33ea 219 11 directed direct VBN cord-021063-4y8m33ea 219 12 to to IN cord-021063-4y8m33ea 219 13 a a DT cord-021063-4y8m33ea 219 14 subset subset NN cord-021063-4y8m33ea 219 15 of of IN cord-021063-4y8m33ea 219 16 cells cell NNS cord-021063-4y8m33ea 219 17 within within IN cord-021063-4y8m33ea 219 18 an an DT cord-021063-4y8m33ea 219 19 organism organism NN cord-021063-4y8m33ea 219 20 . . . cord-021063-4y8m33ea 220 1 First first RB cord-021063-4y8m33ea 220 2 , , , cord-021063-4y8m33ea 220 3 the the DT cord-021063-4y8m33ea 220 4 liposomes liposome NNS cord-021063-4y8m33ea 220 5 may may MD cord-021063-4y8m33ea 220 6 be be VB cord-021063-4y8m33ea 220 7 introduced introduce VBN cord-021063-4y8m33ea 220 8 into into IN cord-021063-4y8m33ea 220 9 a a DT cord-021063-4y8m33ea 220 10 compartment compartment NN cord-021063-4y8m33ea 220 11 of of IN cord-021063-4y8m33ea 220 12 the the DT cord-021063-4y8m33ea 220 13 body body NN cord-021063-4y8m33ea 220 14 that that WDT cord-021063-4y8m33ea 220 15 is be VBZ cord-021063-4y8m33ea 220 16 sequestered sequester VBN cord-021063-4y8m33ea 220 17 from from IN cord-021063-4y8m33ea 220 18 the the DT cord-021063-4y8m33ea 220 19 general general JJ cord-021063-4y8m33ea 220 20 circulation circulation NN cord-021063-4y8m33ea 220 21 . . . cord-021063-4y8m33ea 221 1 One one CD cord-021063-4y8m33ea 221 2 example example NN cord-021063-4y8m33ea 221 3 of of IN cord-021063-4y8m33ea 221 4 this this DT cord-021063-4y8m33ea 221 5 is be VBZ cord-021063-4y8m33ea 221 6 the the DT cord-021063-4y8m33ea 221 7 addition addition NN cord-021063-4y8m33ea 221 8 of of IN cord-021063-4y8m33ea 221 9 liposomes liposome NNS cord-021063-4y8m33ea 221 10 to to IN cord-021063-4y8m33ea 221 11 the the DT cord-021063-4y8m33ea 221 12 airway airway NN cord-021063-4y8m33ea 221 13 in in IN cord-021063-4y8m33ea 221 14 a a DT cord-021063-4y8m33ea 221 15 fluid fluid NN cord-021063-4y8m33ea 221 16 or or CC cord-021063-4y8m33ea 221 17 an an DT cord-021063-4y8m33ea 221 18 aerosol aerosol NN cord-021063-4y8m33ea 222 1 ( ( -LRB- cord-021063-4y8m33ea 222 2 Hazinski Hazinski NNP cord-021063-4y8m33ea 222 3 et et NNP cord-021063-4y8m33ea 222 4 al al NNP cord-021063-4y8m33ea 222 5 . . NNP cord-021063-4y8m33ea 222 6 , , , cord-021063-4y8m33ea 222 7 1991 1991 CD cord-021063-4y8m33ea 222 8 ; ; : cord-021063-4y8m33ea 222 9 Stribling Stribling NNP cord-021063-4y8m33ea 222 10 et et FW cord-021063-4y8m33ea 222 11 al al NNP cord-021063-4y8m33ea 222 12 . . NNP cord-021063-4y8m33ea 222 13 , , , cord-021063-4y8m33ea 222 14 1992 1992 CD cord-021063-4y8m33ea 222 15 ) ) -RRB- cord-021063-4y8m33ea 222 16 . . . cord-021063-4y8m33ea 223 1 Because because IN cord-021063-4y8m33ea 223 2 liposomes liposome NNS cord-021063-4y8m33ea 223 3 can can MD cord-021063-4y8m33ea 223 4 not not RB cord-021063-4y8m33ea 223 5 cross cross VB cord-021063-4y8m33ea 223 6 the the DT cord-021063-4y8m33ea 223 7 lung lung NN cord-021063-4y8m33ea 223 8 epithelial epithelial JJ cord-021063-4y8m33ea 223 9 barrier barrier NN cord-021063-4y8m33ea 223 10 , , , cord-021063-4y8m33ea 223 11 entrance entrance NN cord-021063-4y8m33ea 223 12 into into IN cord-021063-4y8m33ea 223 13 the the DT cord-021063-4y8m33ea 223 14 general general JJ cord-021063-4y8m33ea 223 15 circulation circulation NN cord-021063-4y8m33ea 223 16 is be VBZ cord-021063-4y8m33ea 223 17 prevented prevent VBN cord-021063-4y8m33ea 223 18 . . . cord-021063-4y8m33ea 224 1 Therefore therefore RB cord-021063-4y8m33ea 224 2 , , , cord-021063-4y8m33ea 224 3 it -PRON- PRP cord-021063-4y8m33ea 224 4 is be VBZ cord-021063-4y8m33ea 224 5 anticipated anticipate VBN cord-021063-4y8m33ea 224 6 that that IN cord-021063-4y8m33ea 224 7 liposome liposome NN cord-021063-4y8m33ea 224 8 vectors vector NNS cord-021063-4y8m33ea 224 9 will will MD cord-021063-4y8m33ea 224 10 transfect transfect VB cord-021063-4y8m33ea 224 11 only only RB cord-021063-4y8m33ea 224 12 those those DT cord-021063-4y8m33ea 224 13 cells cell NNS cord-021063-4y8m33ea 224 14 present present JJ cord-021063-4y8m33ea 224 15 on on IN cord-021063-4y8m33ea 224 16 the the DT cord-021063-4y8m33ea 224 17 epithelial epithelial JJ cord-021063-4y8m33ea 224 18 surface surface NN cord-021063-4y8m33ea 224 19 . . . cord-021063-4y8m33ea 225 1 Another another DT cord-021063-4y8m33ea 225 2 site site NN cord-021063-4y8m33ea 225 3 where where WRB cord-021063-4y8m33ea 225 4 this this DT cord-021063-4y8m33ea 225 5 approach approach NN cord-021063-4y8m33ea 225 6 may may MD cord-021063-4y8m33ea 225 7 be be VB cord-021063-4y8m33ea 225 8 applicable applicable JJ cord-021063-4y8m33ea 225 9 is be VBZ cord-021063-4y8m33ea 225 10 in in IN cord-021063-4y8m33ea 225 11 the the DT cord-021063-4y8m33ea 225 12 central central JJ cord-021063-4y8m33ea 225 13 nervous nervous JJ cord-021063-4y8m33ea 225 14 system system NN cord-021063-4y8m33ea 225 15 ( ( -LRB- cord-021063-4y8m33ea 225 16 CNS CNS NNP cord-021063-4y8m33ea 225 17 ) ) -RRB- cord-021063-4y8m33ea 225 18 . . . cord-021063-4y8m33ea 226 1 In in IN cord-021063-4y8m33ea 226 2 the the DT cord-021063-4y8m33ea 226 3 cerebral cerebral JJ cord-021063-4y8m33ea 226 4 vasculature vasculature NN cord-021063-4y8m33ea 226 5 , , , cord-021063-4y8m33ea 226 6 blood blood NN cord-021063-4y8m33ea 226 7 is be VBZ cord-021063-4y8m33ea 226 8 separated separate VBN cord-021063-4y8m33ea 226 9 from from IN cord-021063-4y8m33ea 226 10 the the DT cord-021063-4y8m33ea 226 11 CNS CNS NNP cord-021063-4y8m33ea 226 12 by by IN cord-021063-4y8m33ea 226 13 the the DT cord-021063-4y8m33ea 226 14 blood blood NN cord-021063-4y8m33ea 226 15 - - HYPH cord-021063-4y8m33ea 226 16 brain brain NN cord-021063-4y8m33ea 226 17 barrier barrier NN cord-021063-4y8m33ea 226 18 , , , cord-021063-4y8m33ea 226 19 which which WDT cord-021063-4y8m33ea 226 20 would would MD cord-021063-4y8m33ea 226 21 normally normally RB cord-021063-4y8m33ea 226 22 be be VB cord-021063-4y8m33ea 226 23 completely completely RB cord-021063-4y8m33ea 226 24 impermeable impermeable JJ cord-021063-4y8m33ea 226 25 to to IN cord-021063-4y8m33ea 226 26 any any DT cord-021063-4y8m33ea 226 27 liposomes liposome NNS cord-021063-4y8m33ea 226 28 . . . cord-021063-4y8m33ea 227 1 However however RB cord-021063-4y8m33ea 227 2 , , , cord-021063-4y8m33ea 227 3 if if IN cord-021063-4y8m33ea 227 4 the the DT cord-021063-4y8m33ea 227 5 cerebral cerebral JJ cord-021063-4y8m33ea 227 6 vasculature vasculature NN cord-021063-4y8m33ea 227 7 is be VBZ cord-021063-4y8m33ea 227 8 isolated isolate VBN cord-021063-4y8m33ea 227 9 , , , cord-021063-4y8m33ea 227 10 and and CC cord-021063-4y8m33ea 227 11 perfused perfuse VBN cord-021063-4y8m33ea 227 12 with with IN cord-021063-4y8m33ea 227 13 a a DT cord-021063-4y8m33ea 227 14 hyperosmotic hyperosmotic JJ cord-021063-4y8m33ea 227 15 solution solution NN cord-021063-4y8m33ea 227 16 , , , cord-021063-4y8m33ea 227 17 the the DT cord-021063-4y8m33ea 227 18 blood blood NN cord-021063-4y8m33ea 227 19 - - HYPH cord-021063-4y8m33ea 227 20 brain brain NN cord-021063-4y8m33ea 227 21 barrier barrier NN cord-021063-4y8m33ea 227 22 is be VBZ cord-021063-4y8m33ea 227 23 damaged damage VBN cord-021063-4y8m33ea 227 24 , , , cord-021063-4y8m33ea 227 25 leaving leave VBG cord-021063-4y8m33ea 227 26 holes hole NNS cord-021063-4y8m33ea 227 27 large large JJ cord-021063-4y8m33ea 227 28 enough enough RB cord-021063-4y8m33ea 227 29 to to TO cord-021063-4y8m33ea 227 30 admit admit VB cord-021063-4y8m33ea 227 31 liposomes liposome NNS cord-021063-4y8m33ea 227 32 into into IN cord-021063-4y8m33ea 227 33 the the DT cord-021063-4y8m33ea 227 34 CNS CNS NNP cord-021063-4y8m33ea 227 35 ( ( -LRB- cord-021063-4y8m33ea 227 36 Johansson Johansson NNP cord-021063-4y8m33ea 227 37 , , , cord-021063-4y8m33ea 227 38 1992 1992 CD cord-021063-4y8m33ea 227 39 ) ) -RRB- cord-021063-4y8m33ea 227 40 . . . cord-021063-4y8m33ea 228 1 The the DT cord-021063-4y8m33ea 228 2 blood blood NN cord-021063-4y8m33ea 228 3 - - HYPH cord-021063-4y8m33ea 228 4 brain brain NN cord-021063-4y8m33ea 228 5 barrier barrier NN cord-021063-4y8m33ea 228 6 reconstitutes reconstitute VBZ cord-021063-4y8m33ea 228 7 itself -PRON- PRP cord-021063-4y8m33ea 228 8 shortly shortly RB cord-021063-4y8m33ea 228 9 thereafter thereafter RB cord-021063-4y8m33ea 228 10 , , , cord-021063-4y8m33ea 228 11 leaving leave VBG cord-021063-4y8m33ea 228 12 the the DT cord-021063-4y8m33ea 228 13 liposomes liposome NNS cord-021063-4y8m33ea 228 14 trapped trap VBN cord-021063-4y8m33ea 228 15 within within IN cord-021063-4y8m33ea 228 16 the the DT cord-021063-4y8m33ea 228 17 CNS CNS NNP cord-021063-4y8m33ea 228 18 and and CC cord-021063-4y8m33ea 228 19 unable unable JJ cord-021063-4y8m33ea 228 20 to to TO cord-021063-4y8m33ea 228 21 interact interact VB cord-021063-4y8m33ea 228 22 with with IN cord-021063-4y8m33ea 228 23 any any DT cord-021063-4y8m33ea 228 24 other other JJ cord-021063-4y8m33ea 228 25 cells cell NNS cord-021063-4y8m33ea 228 26 . . . cord-021063-4y8m33ea 229 1 May May MD cord-021063-4y8m33ea 229 2 not not RB cord-021063-4y8m33ea 229 3 be be VB cord-021063-4y8m33ea 229 4 specific specific JJ cord-021063-4y8m33ea 229 5 enough enough JJ cord-021063-4y8m33ea 229 6 Second second JJ cord-021063-4y8m33ea 229 7 , , , cord-021063-4y8m33ea 229 8 the the DT cord-021063-4y8m33ea 229 9 lipid lipid NN cord-021063-4y8m33ea 229 10 composition composition NN cord-021063-4y8m33ea 229 11 of of IN cord-021063-4y8m33ea 229 12 the the DT cord-021063-4y8m33ea 229 13 vesicles vesicle NNS cord-021063-4y8m33ea 229 14 can can MD cord-021063-4y8m33ea 229 15 be be VB cord-021063-4y8m33ea 229 16 adjusted adjust VBN cord-021063-4y8m33ea 229 17 to to TO cord-021063-4y8m33ea 229 18 cause cause VB cord-021063-4y8m33ea 229 19 them -PRON- PRP cord-021063-4y8m33ea 229 20 to to TO cord-021063-4y8m33ea 229 21 be be VB cord-021063-4y8m33ea 229 22 taken take VBN cord-021063-4y8m33ea 229 23 up up RP cord-021063-4y8m33ea 229 24 preferentially preferentially RB cord-021063-4y8m33ea 229 25 by by IN cord-021063-4y8m33ea 229 26 some some DT cord-021063-4y8m33ea 229 27 types type NNS cord-021063-4y8m33ea 229 28 of of IN cord-021063-4y8m33ea 229 29 cells cell NNS cord-021063-4y8m33ea 229 30 . . . cord-021063-4y8m33ea 230 1 For for IN cord-021063-4y8m33ea 230 2 example example NN cord-021063-4y8m33ea 230 3 , , , cord-021063-4y8m33ea 230 4 macrophages macrophage NNS cord-021063-4y8m33ea 230 5 have have VBP cord-021063-4y8m33ea 230 6 a a DT cord-021063-4y8m33ea 230 7 very very RB cord-021063-4y8m33ea 230 8 high high JJ cord-021063-4y8m33ea 230 9 affinity affinity NN cord-021063-4y8m33ea 230 10 for for IN cord-021063-4y8m33ea 230 11 liposomes liposome NNS cord-021063-4y8m33ea 230 12 containing contain VBG cord-021063-4y8m33ea 230 13 ( ( -LRB- cord-021063-4y8m33ea 230 14 PS PS NNP cord-021063-4y8m33ea 230 15 ) ) -RRB- cord-021063-4y8m33ea 230 16 on on IN cord-021063-4y8m33ea 230 17 their -PRON- PRP$ cord-021063-4y8m33ea 230 18 surface surface NN cord-021063-4y8m33ea 231 1 ( ( -LRB- cord-021063-4y8m33ea 231 2 Lee Lee NNP cord-021063-4y8m33ea 231 3 et et NNP cord-021063-4y8m33ea 231 4 al al NNP cord-021063-4y8m33ea 231 5 . . NNP cord-021063-4y8m33ea 231 6 , , , cord-021063-4y8m33ea 231 7 1992 1992 CD cord-021063-4y8m33ea 231 8 ) ) -RRB- cord-021063-4y8m33ea 231 9 . . . cord-021063-4y8m33ea 232 1 Consequently consequently RB cord-021063-4y8m33ea 232 2 , , , cord-021063-4y8m33ea 232 3 liposomes liposome NNS cord-021063-4y8m33ea 232 4 containing contain VBG cord-021063-4y8m33ea 232 5 a a DT cord-021063-4y8m33ea 232 6 substantial substantial JJ cord-021063-4y8m33ea 232 7 fraction fraction NN cord-021063-4y8m33ea 232 8 of of IN cord-021063-4y8m33ea 232 9 PS PS NNP cord-021063-4y8m33ea 232 10 are be VBP cord-021063-4y8m33ea 232 11 quickly quickly RB cord-021063-4y8m33ea 232 12 cleared clear VBN cord-021063-4y8m33ea 232 13 from from IN cord-021063-4y8m33ea 232 14 the the DT cord-021063-4y8m33ea 232 15 circulation circulation NN cord-021063-4y8m33ea 232 16 by by IN cord-021063-4y8m33ea 232 17 macrophages macrophage NNS cord-021063-4y8m33ea 232 18 ( ( -LRB- cord-021063-4y8m33ea 232 19 Allen Allen NNP cord-021063-4y8m33ea 232 20 et et NNP cord-021063-4y8m33ea 232 21 al al NNP cord-021063-4y8m33ea 232 22 . . NNP cord-021063-4y8m33ea 232 23 , , , cord-021063-4y8m33ea 232 24 1989 1989 CD cord-021063-4y8m33ea 232 25 ) ) -RRB- cord-021063-4y8m33ea 232 26 . . . cord-021063-4y8m33ea 233 1 A a DT cord-021063-4y8m33ea 233 2 similar similar JJ cord-021063-4y8m33ea 233 3 targeting target VBG cord-021063-4y8m33ea 233 4 strategy strategy NN cord-021063-4y8m33ea 233 5 uses use VBZ cord-021063-4y8m33ea 233 6 lactosylceramide lactosylceramide NN cord-021063-4y8m33ea 233 7 as as IN cord-021063-4y8m33ea 233 8 a a DT cord-021063-4y8m33ea 233 9 membrane membrane NN cord-021063-4y8m33ea 233 10 component component NN cord-021063-4y8m33ea 233 11 . . . cord-021063-4y8m33ea 234 1 This this DT cord-021063-4y8m33ea 234 2 lipid lipid NN cord-021063-4y8m33ea 234 3 binds bind VBZ cord-021063-4y8m33ea 234 4 to to IN cord-021063-4y8m33ea 234 5 the the DT cord-021063-4y8m33ea 234 6 asialoglycoprotein asialoglycoprotein NNP cord-021063-4y8m33ea 234 7 receptors receptor NNS cord-021063-4y8m33ea 234 8 found find VBN cord-021063-4y8m33ea 234 9 on on IN cord-021063-4y8m33ea 234 10 hepatocytes hepatocyte NNS cord-021063-4y8m33ea 234 11 , , , cord-021063-4y8m33ea 234 12 causing cause VBG cord-021063-4y8m33ea 234 13 these these DT cord-021063-4y8m33ea 234 14 cells cell NNS cord-021063-4y8m33ea 234 15 to to TO cord-021063-4y8m33ea 234 16 be be VB cord-021063-4y8m33ea 234 17 preferentially preferentially RB cord-021063-4y8m33ea 234 18 targeted target VBN cord-021063-4y8m33ea 234 19 by by IN cord-021063-4y8m33ea 234 20 the the DT cord-021063-4y8m33ea 234 21 vesicles vesicle NNS cord-021063-4y8m33ea 234 22 ( ( -LRB- cord-021063-4y8m33ea 234 23 Grosse Grosse NNP cord-021063-4y8m33ea 234 24 et et FW cord-021063-4y8m33ea 234 25 al al NNP cord-021063-4y8m33ea 234 26 . . NNP cord-021063-4y8m33ea 234 27 , , , cord-021063-4y8m33ea 234 28 1984 1984 CD cord-021063-4y8m33ea 234 29 ) ) -RRB- cord-021063-4y8m33ea 234 30 . . . cord-021063-4y8m33ea 235 1 The the DT cord-021063-4y8m33ea 235 2 final final JJ cord-021063-4y8m33ea 235 3 method method NN cord-021063-4y8m33ea 235 4 involves involve VBZ cord-021063-4y8m33ea 235 5 the the DT cord-021063-4y8m33ea 235 6 addition addition NN cord-021063-4y8m33ea 235 7 of of IN cord-021063-4y8m33ea 235 8 antibodies antibody NNS cord-021063-4y8m33ea 235 9 or or CC cord-021063-4y8m33ea 235 10 other other JJ cord-021063-4y8m33ea 235 11 proteins protein NNS cord-021063-4y8m33ea 235 12 to to IN cord-021063-4y8m33ea 235 13 the the DT cord-021063-4y8m33ea 235 14 surface surface NN cord-021063-4y8m33ea 235 15 of of IN cord-021063-4y8m33ea 235 16 the the DT cord-021063-4y8m33ea 235 17 liposome liposome NN cord-021063-4y8m33ea 235 18 after after IN cord-021063-4y8m33ea 235 19 it -PRON- PRP cord-021063-4y8m33ea 235 20 has have VBZ cord-021063-4y8m33ea 235 21 been be VBN cord-021063-4y8m33ea 235 22 formed form VBN cord-021063-4y8m33ea 235 23 ( ( -LRB- cord-021063-4y8m33ea 235 24 Loughrey Loughrey NNP cord-021063-4y8m33ea 235 25 et et NNP cord-021063-4y8m33ea 235 26 al al NNP cord-021063-4y8m33ea 235 27 . . NNP cord-021063-4y8m33ea 235 28 , , , cord-021063-4y8m33ea 235 29 1990 1990 CD cord-021063-4y8m33ea 235 30 ) ) -RRB- cord-021063-4y8m33ea 235 31 . . . cord-021063-4y8m33ea 236 1 These these DT cord-021063-4y8m33ea 236 2 " " `` cord-021063-4y8m33ea 236 3 proteoliposomes proteoliposome NNS cord-021063-4y8m33ea 236 4 " " '' cord-021063-4y8m33ea 236 5 are be VBP cord-021063-4y8m33ea 236 6 taken take VBN cord-021063-4y8m33ea 236 7 up up RP cord-021063-4y8m33ea 236 8 by by IN cord-021063-4y8m33ea 236 9 cells cell NNS cord-021063-4y8m33ea 236 10 to to TO cord-021063-4y8m33ea 236 11 which which WDT cord-021063-4y8m33ea 236 12 they -PRON- PRP cord-021063-4y8m33ea 236 13 can can MD cord-021063-4y8m33ea 236 14 bind bind VB cord-021063-4y8m33ea 236 15 . . . cord-021063-4y8m33ea 237 1 Table table NN cord-021063-4y8m33ea 237 2 5 5 CD cord-021063-4y8m33ea 237 3 gives give VBZ cord-021063-4y8m33ea 237 4 a a DT cord-021063-4y8m33ea 237 5 representative representative JJ cord-021063-4y8m33ea 237 6 list list NN cord-021063-4y8m33ea 237 7 of of IN cord-021063-4y8m33ea 237 8 proteins protein NNS cord-021063-4y8m33ea 237 9 that that WDT cord-021063-4y8m33ea 237 10 have have VBP cord-021063-4y8m33ea 237 11 been be VBN cord-021063-4y8m33ea 237 12 used use VBN cord-021063-4y8m33ea 237 13 to to TO cord-021063-4y8m33ea 237 14 target target VB cord-021063-4y8m33ea 237 15 liposomes liposome NNS cord-021063-4y8m33ea 237 16 to to IN cord-021063-4y8m33ea 237 17 cells cell NNS cord-021063-4y8m33ea 237 18 . . . cord-021063-4y8m33ea 238 1 Many many JJ cord-021063-4y8m33ea 238 2 proteins protein NNS cord-021063-4y8m33ea 238 3 can can MD cord-021063-4y8m33ea 238 4 be be VB cord-021063-4y8m33ea 238 5 modified modify VBN cord-021063-4y8m33ea 238 6 by by IN cord-021063-4y8m33ea 238 7 the the DT cord-021063-4y8m33ea 238 8 addition addition NN cord-021063-4y8m33ea 238 9 of of IN cord-021063-4y8m33ea 238 10 phospholipid phospholipid NN cord-021063-4y8m33ea 238 11 molecules molecule NNS cord-021063-4y8m33ea 238 12 or or CC cord-021063-4y8m33ea 238 13 acyl acyl NN cord-021063-4y8m33ea 238 14 chains chain NNS cord-021063-4y8m33ea 238 15 and and CC cord-021063-4y8m33ea 238 16 retain retain VB cord-021063-4y8m33ea 238 17 their -PRON- PRP$ cord-021063-4y8m33ea 238 18 native native JJ cord-021063-4y8m33ea 238 19 function function NN cord-021063-4y8m33ea 238 20 . . . cord-021063-4y8m33ea 239 1 These these DT cord-021063-4y8m33ea 239 2 modified modify VBN cord-021063-4y8m33ea 239 3 proteins protein NNS cord-021063-4y8m33ea 239 4 can can MD cord-021063-4y8m33ea 239 5 be be VB cord-021063-4y8m33ea 239 6 coupled couple VBN cord-021063-4y8m33ea 239 7 to to IN cord-021063-4y8m33ea 239 8 a a DT cord-021063-4y8m33ea 239 9 preexisting preexist VBG cord-021063-4y8m33ea 239 10 bilayer bilayer NN cord-021063-4y8m33ea 239 11 , , , cord-021063-4y8m33ea 239 12 endowing endow VBG cord-021063-4y8m33ea 239 13 the the DT cord-021063-4y8m33ea 239 14 liposome liposome NN cord-021063-4y8m33ea 239 15 with with IN cord-021063-4y8m33ea 239 16 their -PRON- PRP$ cord-021063-4y8m33ea 239 17 binding bind VBG cord-021063-4y8m33ea 239 18 properties property NNS cord-021063-4y8m33ea 239 19 . . . cord-021063-4y8m33ea 240 1 All all DT cord-021063-4y8m33ea 240 2 three three CD cord-021063-4y8m33ea 240 3 methods method NNS cord-021063-4y8m33ea 240 4 described describe VBN cord-021063-4y8m33ea 240 5 above above RB cord-021063-4y8m33ea 240 6 have have VBP cord-021063-4y8m33ea 240 7 been be VBN cord-021063-4y8m33ea 240 8 used use VBN cord-021063-4y8m33ea 240 9 successfully successfully RB cord-021063-4y8m33ea 240 10 to to TO cord-021063-4y8m33ea 240 11 direct direct VB cord-021063-4y8m33ea 240 12 the the DT cord-021063-4y8m33ea 240 13 uptake uptake NN cord-021063-4y8m33ea 240 14 of of IN cord-021063-4y8m33ea 240 15 liposomes liposome NNS cord-021063-4y8m33ea 240 16 to to IN cord-021063-4y8m33ea 240 17 specific specific JJ cord-021063-4y8m33ea 240 18 cell cell NN cord-021063-4y8m33ea 240 19 types type NNS cord-021063-4y8m33ea 240 20 . . . cord-021063-4y8m33ea 241 1 The the DT cord-021063-4y8m33ea 241 2 methods method NNS cord-021063-4y8m33ea 241 3 are be VBP cord-021063-4y8m33ea 241 4 not not RB cord-021063-4y8m33ea 241 5 mutually mutually RB cord-021063-4y8m33ea 241 6 exclusive exclusive JJ cord-021063-4y8m33ea 241 7 and and CC cord-021063-4y8m33ea 241 8 , , , cord-021063-4y8m33ea 241 9 in in IN cord-021063-4y8m33ea 241 10 principle principle NN cord-021063-4y8m33ea 241 11 , , , cord-021063-4y8m33ea 241 12 it -PRON- PRP cord-021063-4y8m33ea 241 13 should should MD cord-021063-4y8m33ea 241 14 be be VB cord-021063-4y8m33ea 241 15 possible possible JJ cord-021063-4y8m33ea 241 16 to to TO cord-021063-4y8m33ea 241 17 combine combine VB cord-021063-4y8m33ea 241 18 them -PRON- PRP cord-021063-4y8m33ea 241 19 for for IN cord-021063-4y8m33ea 241 20 more more RBR cord-021063-4y8m33ea 241 21 specific specific JJ cord-021063-4y8m33ea 241 22 targeting targeting NN cord-021063-4y8m33ea 241 23 . . . cord-021063-4y8m33ea 242 1 The the DT cord-021063-4y8m33ea 242 2 central central JJ cord-021063-4y8m33ea 242 3 problem problem NN cord-021063-4y8m33ea 242 4 of of IN cord-021063-4y8m33ea 242 5 any any DT cord-021063-4y8m33ea 242 6 liposome liposome NN cord-021063-4y8m33ea 242 7 - - HYPH cord-021063-4y8m33ea 242 8 based base VBN cord-021063-4y8m33ea 242 9 gene gene NN cord-021063-4y8m33ea 242 10 therapy therapy NN cord-021063-4y8m33ea 242 11 system system NN cord-021063-4y8m33ea 242 12 is be VBZ cord-021063-4y8m33ea 242 13 that that IN cord-021063-4y8m33ea 242 14 DNA DNA NNP cord-021063-4y8m33ea 242 15 must must MD cord-021063-4y8m33ea 242 16 be be VB cord-021063-4y8m33ea 242 17 introduced introduce VBN cord-021063-4y8m33ea 242 18 into into IN cord-021063-4y8m33ea 242 19 the the DT cord-021063-4y8m33ea 242 20 cytoplasm cytoplasm NN cord-021063-4y8m33ea 242 21 of of IN cord-021063-4y8m33ea 242 22 the the DT cord-021063-4y8m33ea 242 23 target target NN cord-021063-4y8m33ea 242 24 cell cell NN cord-021063-4y8m33ea 242 25 . . . cord-021063-4y8m33ea 243 1 When when WRB cord-021063-4y8m33ea 243 2 DNA dna NN cord-021063-4y8m33ea 243 3 - - HYPH cord-021063-4y8m33ea 243 4 loaded load VBN cord-021063-4y8m33ea 243 5 liposomes liposome NNS cord-021063-4y8m33ea 243 6 are be VBP cord-021063-4y8m33ea 243 7 added add VBN cord-021063-4y8m33ea 243 8 to to IN cord-021063-4y8m33ea 243 9 cells cell NNS cord-021063-4y8m33ea 243 10 they -PRON- PRP cord-021063-4y8m33ea 243 11 are be VBP cord-021063-4y8m33ea 243 12 endocytosed endocytose VBN cord-021063-4y8m33ea 243 13 , , , cord-021063-4y8m33ea 243 14 and and CC cord-021063-4y8m33ea 243 15 most most JJS cord-021063-4y8m33ea 243 16 are be VBP cord-021063-4y8m33ea 243 17 carried carry VBN cord-021063-4y8m33ea 243 18 to to IN cord-021063-4y8m33ea 243 19 lysosomes lysosome NNS cord-021063-4y8m33ea 243 20 where where WRB cord-021063-4y8m33ea 243 21 they -PRON- PRP cord-021063-4y8m33ea 243 22 are be VBP cord-021063-4y8m33ea 243 23 degraded degrade VBN cord-021063-4y8m33ea 243 24 by by IN cord-021063-4y8m33ea 243 25 digestive digestive JJ cord-021063-4y8m33ea 243 26 enzymes enzyme NNS cord-021063-4y8m33ea 243 27 . . . cord-021063-4y8m33ea 244 1 Somehow somehow RB cord-021063-4y8m33ea 244 2 , , , cord-021063-4y8m33ea 244 3 a a DT cord-021063-4y8m33ea 244 4 small small JJ cord-021063-4y8m33ea 244 5 fraction fraction NN cord-021063-4y8m33ea 244 6 of of IN cord-021063-4y8m33ea 244 7 encapsulated encapsulate VBN cord-021063-4y8m33ea 244 8 DNA dna NN cord-021063-4y8m33ea 244 9 escapes escape VBZ cord-021063-4y8m33ea 244 10 this this DT cord-021063-4y8m33ea 244 11 pathway pathway NN cord-021063-4y8m33ea 244 12 , , , cord-021063-4y8m33ea 244 13 enters enter VBZ cord-021063-4y8m33ea 244 14 the the DT cord-021063-4y8m33ea 244 15 cytoplasm cytoplasm NN cord-021063-4y8m33ea 244 16 , , , cord-021063-4y8m33ea 244 17 and and CC cord-021063-4y8m33ea 244 18 is be VBZ cord-021063-4y8m33ea 244 19 expressed express VBN cord-021063-4y8m33ea 244 20 by by IN cord-021063-4y8m33ea 244 21 the the DT cord-021063-4y8m33ea 244 22 cells cell NNS cord-021063-4y8m33ea 244 23 ( ( -LRB- cord-021063-4y8m33ea 244 24 Straubinger Straubinger NNP cord-021063-4y8m33ea 244 25 et et NNP cord-021063-4y8m33ea 244 26 al al NNP cord-021063-4y8m33ea 244 27 . . NNP cord-021063-4y8m33ea 244 28 , , , cord-021063-4y8m33ea 244 29 1990 1990 CD cord-021063-4y8m33ea 244 30 ) ) -RRB- cord-021063-4y8m33ea 244 31 . . . cord-021063-4y8m33ea 245 1 Several several JJ cord-021063-4y8m33ea 245 2 methods method NNS cord-021063-4y8m33ea 245 3 have have VBP cord-021063-4y8m33ea 245 4 been be VBN cord-021063-4y8m33ea 245 5 developed develop VBN cord-021063-4y8m33ea 245 6 to to TO cord-021063-4y8m33ea 245 7 increase increase VB cord-021063-4y8m33ea 245 8 the the DT cord-021063-4y8m33ea 245 9 proportion proportion NN cord-021063-4y8m33ea 245 10 of of IN cord-021063-4y8m33ea 245 11 DNA dna NN cord-021063-4y8m33ea 245 12 delivered deliver VBN cord-021063-4y8m33ea 245 13 to to IN cord-021063-4y8m33ea 245 14 the the DT cord-021063-4y8m33ea 245 15 cytosol cytosol NN cord-021063-4y8m33ea 245 16 . . . cord-021063-4y8m33ea 246 1 Two two CD cord-021063-4y8m33ea 246 2 general general JJ cord-021063-4y8m33ea 246 3 approaches approach NNS cord-021063-4y8m33ea 246 4 that that WDT cord-021063-4y8m33ea 246 5 have have VBP cord-021063-4y8m33ea 246 6 been be VBN cord-021063-4y8m33ea 246 7 used use VBN cord-021063-4y8m33ea 246 8 successfully successfully RB cord-021063-4y8m33ea 246 9 are be VBP cord-021063-4y8m33ea 246 10 : : : cord-021063-4y8m33ea 246 11 ( ( -LRB- cord-021063-4y8m33ea 246 12 i i NN cord-021063-4y8m33ea 246 13 ) ) -RRB- cord-021063-4y8m33ea 246 14 bypassing bypass VBG cord-021063-4y8m33ea 246 15 the the DT cord-021063-4y8m33ea 246 16 endocytic endocytic JJ cord-021063-4y8m33ea 246 17 pathway pathway NN cord-021063-4y8m33ea 246 18 completely completely RB cord-021063-4y8m33ea 246 19 , , , cord-021063-4y8m33ea 246 20 and and CC cord-021063-4y8m33ea 246 21 ( ( -LRB- cord-021063-4y8m33ea 246 22 ii ii NN cord-021063-4y8m33ea 246 23 ) ) -RRB- cord-021063-4y8m33ea 246 24 using use VBG cord-021063-4y8m33ea 246 25 the the DT cord-021063-4y8m33ea 246 26 initial initial JJ cord-021063-4y8m33ea 246 27 stages stage NNS cord-021063-4y8m33ea 246 28 of of IN cord-021063-4y8m33ea 246 29 the the DT cord-021063-4y8m33ea 246 30 endocytic endocytic JJ cord-021063-4y8m33ea 246 31 pathway pathway NN cord-021063-4y8m33ea 246 32 but but CC cord-021063-4y8m33ea 246 33 escaping escape VBG cord-021063-4y8m33ea 246 34 the the DT cord-021063-4y8m33ea 246 35 pathway pathway NN cord-021063-4y8m33ea 246 36 before before IN cord-021063-4y8m33ea 246 37 delivery delivery NN cord-021063-4y8m33ea 246 38 of of IN cord-021063-4y8m33ea 246 39 the the DT cord-021063-4y8m33ea 246 40 DNA dna NN cord-021063-4y8m33ea 246 41 to to IN cord-021063-4y8m33ea 246 42 lysosomes lysosome NNS cord-021063-4y8m33ea 246 43 . . . cord-021063-4y8m33ea 247 1 The the DT cord-021063-4y8m33ea 247 2 endocytic endocytic JJ cord-021063-4y8m33ea 247 3 pathway pathway NN cord-021063-4y8m33ea 247 4 of of IN cord-021063-4y8m33ea 247 5 liposomal liposomal JJ cord-021063-4y8m33ea 247 6 DNA dna NN cord-021063-4y8m33ea 247 7 entry entry NN cord-021063-4y8m33ea 247 8 into into IN cord-021063-4y8m33ea 247 9 the the DT cord-021063-4y8m33ea 247 10 cell cell NN cord-021063-4y8m33ea 247 11 is be VBZ cord-021063-4y8m33ea 247 12 bypassed bypass VBN cord-021063-4y8m33ea 247 13 when when WRB cord-021063-4y8m33ea 247 14 liposomes liposome NNS cord-021063-4y8m33ea 247 15 are be VBP cord-021063-4y8m33ea 247 16 fused fuse VBN cord-021063-4y8m33ea 247 17 directly directly RB cord-021063-4y8m33ea 247 18 to to IN cord-021063-4y8m33ea 247 19 the the DT cord-021063-4y8m33ea 247 20 plasma plasma NN cord-021063-4y8m33ea 247 21 membrane membrane NN cord-021063-4y8m33ea 247 22 of of IN cord-021063-4y8m33ea 247 23 the the DT cord-021063-4y8m33ea 247 24 cell cell NN cord-021063-4y8m33ea 247 25 . . . cord-021063-4y8m33ea 248 1 This this DT cord-021063-4y8m33ea 248 2 has have VBZ cord-021063-4y8m33ea 248 3 been be VBN cord-021063-4y8m33ea 248 4 accomplished accomplish VBN cord-021063-4y8m33ea 248 5 using use VBG cord-021063-4y8m33ea 248 6 virosomes virosome NNS cord-021063-4y8m33ea 248 7 containing contain VBG cord-021063-4y8m33ea 248 8 a a DT cord-021063-4y8m33ea 248 9 constitutively constitutively RB cord-021063-4y8m33ea 248 10 active active JJ cord-021063-4y8m33ea 248 11 viral viral JJ cord-021063-4y8m33ea 248 12 fusion fusion NN cord-021063-4y8m33ea 248 13 protein protein NN cord-021063-4y8m33ea 248 14 ( ( -LRB- cord-021063-4y8m33ea 248 15 Nakanishi Nakanishi NNP cord-021063-4y8m33ea 248 16 et et NNP cord-021063-4y8m33ea 248 17 al al NNP cord-021063-4y8m33ea 248 18 . . NNP cord-021063-4y8m33ea 248 19 , , , cord-021063-4y8m33ea 248 20 1987 1987 CD cord-021063-4y8m33ea 248 21 ) ) -RRB- cord-021063-4y8m33ea 248 22 . . . cord-021063-4y8m33ea 249 1 As as RB cord-021063-4y8m33ea 249 2 soon soon RB cord-021063-4y8m33ea 249 3 as as IN cord-021063-4y8m33ea 249 4 the the DT cord-021063-4y8m33ea 249 5 virosome virosome NN cord-021063-4y8m33ea 249 6 binds bind VBZ cord-021063-4y8m33ea 249 7 to to IN cord-021063-4y8m33ea 249 8 the the DT cord-021063-4y8m33ea 249 9 cell cell NN cord-021063-4y8m33ea 249 10 surface surface NN cord-021063-4y8m33ea 249 11 , , , cord-021063-4y8m33ea 249 12 the the DT cord-021063-4y8m33ea 249 13 fusion fusion NN cord-021063-4y8m33ea 249 14 protein protein NN cord-021063-4y8m33ea 249 15 acts act VBZ cord-021063-4y8m33ea 249 16 to to TO cord-021063-4y8m33ea 249 17 fuse fuse VB cord-021063-4y8m33ea 249 18 the the DT cord-021063-4y8m33ea 249 19 virosomal virosomal JJ cord-021063-4y8m33ea 249 20 membrane membrane NN cord-021063-4y8m33ea 249 21 with with IN cord-021063-4y8m33ea 249 22 that that DT cord-021063-4y8m33ea 249 23 of of IN cord-021063-4y8m33ea 249 24 the the DT cord-021063-4y8m33ea 249 25 cell cell NN cord-021063-4y8m33ea 249 26 , , , cord-021063-4y8m33ea 249 27 causing cause VBG cord-021063-4y8m33ea 249 28 the the DT cord-021063-4y8m33ea 249 29 vesicle vesicle NN cord-021063-4y8m33ea 249 30 contents content NNS cord-021063-4y8m33ea 249 31 to to TO cord-021063-4y8m33ea 249 32 be be VB cord-021063-4y8m33ea 249 33 introduced introduce VBN cord-021063-4y8m33ea 249 34 directly directly RB cord-021063-4y8m33ea 249 35 into into IN cord-021063-4y8m33ea 249 36 the the DT cord-021063-4y8m33ea 249 37 cytoplasm cytoplasm NN cord-021063-4y8m33ea 249 38 . . . cord-021063-4y8m33ea 250 1 Some some DT cord-021063-4y8m33ea 250 2 liposome liposome NN cord-021063-4y8m33ea 250 3 delivery delivery NN cord-021063-4y8m33ea 250 4 systems system NNS cord-021063-4y8m33ea 250 5 use use VBP cord-021063-4y8m33ea 250 6 the the DT cord-021063-4y8m33ea 250 7 initial initial JJ cord-021063-4y8m33ea 250 8 stages stage NNS cord-021063-4y8m33ea 250 9 of of IN cord-021063-4y8m33ea 250 10 the the DT cord-021063-4y8m33ea 250 11 endocytic endocytic JJ cord-021063-4y8m33ea 250 12 pathway pathway NN cord-021063-4y8m33ea 250 13 in in IN cord-021063-4y8m33ea 250 14 the the DT cord-021063-4y8m33ea 250 15 delivery delivery NN cord-021063-4y8m33ea 250 16 process process NN cord-021063-4y8m33ea 250 17 . . . cord-021063-4y8m33ea 251 1 This this DT cord-021063-4y8m33ea 251 2 strategy strategy NN cord-021063-4y8m33ea 251 3 takes take VBZ cord-021063-4y8m33ea 251 4 advantage advantage NN cord-021063-4y8m33ea 251 5 of of IN cord-021063-4y8m33ea 251 6 the the DT cord-021063-4y8m33ea 251 7 low low JJ cord-021063-4y8m33ea 251 8 pH ph NN cord-021063-4y8m33ea 251 9 of of IN cord-021063-4y8m33ea 251 10 endosomes endosome NNS cord-021063-4y8m33ea 251 11 , , , cord-021063-4y8m33ea 251 12 which which WDT cord-021063-4y8m33ea 251 13 can can MD cord-021063-4y8m33ea 251 14 be be VB cord-021063-4y8m33ea 251 15 used use VBN cord-021063-4y8m33ea 251 16 to to TO cord-021063-4y8m33ea 251 17 trigger trigger VB cord-021063-4y8m33ea 251 18 fusion fusion NN cord-021063-4y8m33ea 251 19 of of IN cord-021063-4y8m33ea 251 20 liposomes liposome NNS cord-021063-4y8m33ea 251 21 with with IN cord-021063-4y8m33ea 251 22 the the DT cord-021063-4y8m33ea 251 23 endosomal endosomal NNP cord-021063-4y8m33ea 251 24 membrane membrane NN cord-021063-4y8m33ea 251 25 . . . cord-021063-4y8m33ea 252 1 pH ph JJ cord-021063-4y8m33ea 252 2 - - HYPH cord-021063-4y8m33ea 252 3 dependent dependent JJ cord-021063-4y8m33ea 252 4 fusion fusion NN cord-021063-4y8m33ea 252 5 of of IN cord-021063-4y8m33ea 252 6 liposomes liposome NNS cord-021063-4y8m33ea 252 7 with with IN cord-021063-4y8m33ea 252 8 endosomes endosome NNS cord-021063-4y8m33ea 252 9 has have VBZ cord-021063-4y8m33ea 252 10 been be VBN cord-021063-4y8m33ea 252 11 achieved achieve VBN cord-021063-4y8m33ea 252 12 using use VBG cord-021063-4y8m33ea 252 13 vesicles vesicle NNS cord-021063-4y8m33ea 252 14 composed compose VBN cord-021063-4y8m33ea 252 15 of of IN cord-021063-4y8m33ea 252 16 phosphatidylethanolamine phosphatidylethanolamine JJ cord-021063-4y8m33ea 252 17 ( ( -LRB- cord-021063-4y8m33ea 252 18 PE PE NNP cord-021063-4y8m33ea 252 19 ) ) -RRB- cord-021063-4y8m33ea 252 20 and and CC cord-021063-4y8m33ea 252 21 substances substance NNS cord-021063-4y8m33ea 252 22 such such JJ cord-021063-4y8m33ea 252 23 as as IN cord-021063-4y8m33ea 252 24 dipalmitoylsuccinylglycerol dipalmitoylsuccinylglycerol NNP cord-021063-4y8m33ea 252 25 that that WDT cord-021063-4y8m33ea 252 26 leave leave VBP cord-021063-4y8m33ea 252 27 the the DT cord-021063-4y8m33ea 252 28 membrane membrane NN cord-021063-4y8m33ea 252 29 at at IN cord-021063-4y8m33ea 252 30 low low JJ cord-021063-4y8m33ea 252 31 pH ph NN cord-021063-4y8m33ea 253 1 ( ( -LRB- cord-021063-4y8m33ea 253 2 Liu Liu NNP cord-021063-4y8m33ea 253 3 and and CC cord-021063-4y8m33ea 253 4 Huang Huang NNP cord-021063-4y8m33ea 253 5 , , , cord-021063-4y8m33ea 253 6 1990 1990 CD cord-021063-4y8m33ea 253 7 ) ) -RRB- cord-021063-4y8m33ea 253 8 . . . cord-021063-4y8m33ea 254 1 As as IN cord-021063-4y8m33ea 254 2 the the DT cord-021063-4y8m33ea 254 3 pH pH NNP cord-021063-4y8m33ea 254 4 is be VBZ cord-021063-4y8m33ea 254 5 lowered lower VBN cord-021063-4y8m33ea 254 6 in in IN cord-021063-4y8m33ea 254 7 the the DT cord-021063-4y8m33ea 254 8 endosome endosome NN cord-021063-4y8m33ea 254 9 , , , cord-021063-4y8m33ea 254 10 the the DT cord-021063-4y8m33ea 254 11 effective effective JJ cord-021063-4y8m33ea 254 12 concentration concentration NN cord-021063-4y8m33ea 254 13 of of IN cord-021063-4y8m33ea 254 14 PE PE NNP cord-021063-4y8m33ea 254 15 rises rise NNS cord-021063-4y8m33ea 254 16 . . . cord-021063-4y8m33ea 255 1 When when WRB cord-021063-4y8m33ea 255 2 the the DT cord-021063-4y8m33ea 255 3 concentration concentration NN cord-021063-4y8m33ea 255 4 rises rise VBZ cord-021063-4y8m33ea 255 5 above above IN cord-021063-4y8m33ea 255 6 60 60 CD cord-021063-4y8m33ea 255 7 mole mole NN cord-021063-4y8m33ea 255 8 percent percent NN cord-021063-4y8m33ea 255 9 , , , cord-021063-4y8m33ea 255 10 the the DT cord-021063-4y8m33ea 255 11 vesicle vesicle NN cord-021063-4y8m33ea 255 12 membrane membrane NN cord-021063-4y8m33ea 255 13 can can MD cord-021063-4y8m33ea 255 14 no no RB cord-021063-4y8m33ea 255 15 longer longer RB cord-021063-4y8m33ea 255 16 remain remain VB cord-021063-4y8m33ea 255 17 as as IN cord-021063-4y8m33ea 255 18 a a DT cord-021063-4y8m33ea 255 19 bilayer bilayer NN cord-021063-4y8m33ea 255 20 . . . cord-021063-4y8m33ea 256 1 As as IN cord-021063-4y8m33ea 256 2 it -PRON- PRP cord-021063-4y8m33ea 256 3 converts convert VBZ cord-021063-4y8m33ea 256 4 to to IN cord-021063-4y8m33ea 256 5 the the DT cord-021063-4y8m33ea 256 6 inverted inverted JJ cord-021063-4y8m33ea 256 7 hexagonal hexagonal JJ cord-021063-4y8m33ea 256 8 phase phase NN cord-021063-4y8m33ea 256 9 , , , cord-021063-4y8m33ea 256 10 it -PRON- PRP cord-021063-4y8m33ea 256 11 destabilizes destabilize VBZ cord-021063-4y8m33ea 256 12 the the DT cord-021063-4y8m33ea 256 13 adjacent adjacent JJ cord-021063-4y8m33ea 256 14 endosomal endosomal NNP cord-021063-4y8m33ea 256 15 membrane membrane NN cord-021063-4y8m33ea 256 16 , , , cord-021063-4y8m33ea 256 17 and and CC cord-021063-4y8m33ea 256 18 releases release VBZ cord-021063-4y8m33ea 256 19 the the DT cord-021063-4y8m33ea 256 20 liposomal liposomal JJ cord-021063-4y8m33ea 256 21 contents content NNS cord-021063-4y8m33ea 256 22 into into IN cord-021063-4y8m33ea 256 23 the the DT cord-021063-4y8m33ea 256 24 cytoplasm cytoplasm NN cord-021063-4y8m33ea 256 25 . . . cord-021063-4y8m33ea 257 1 Similar similar JJ cord-021063-4y8m33ea 257 2 results result NNS cord-021063-4y8m33ea 257 3 can can MD cord-021063-4y8m33ea 257 4 be be VB cord-021063-4y8m33ea 257 5 seen see VBN cord-021063-4y8m33ea 257 6 using use VBG cord-021063-4y8m33ea 257 7 virosomes virosomes NN cord-021063-4y8m33ea 257 8 containing contain VBG cord-021063-4y8m33ea 257 9 pH ph JJ cord-021063-4y8m33ea 257 10 - - HYPH cord-021063-4y8m33ea 257 11 sensitive sensitive JJ cord-021063-4y8m33ea 257 12 fusion fusion NN cord-021063-4y8m33ea 257 13 proteins protein NNS cord-021063-4y8m33ea 258 1 ( ( -LRB- cord-021063-4y8m33ea 258 2 Gould Gould NNP cord-021063-4y8m33ea 258 3 - - HYPH cord-021063-4y8m33ea 258 4 Fogerite Fogerite NNP cord-021063-4y8m33ea 258 5 et et NNP cord-021063-4y8m33ea 258 6 al al NNP cord-021063-4y8m33ea 258 7 . . NNP cord-021063-4y8m33ea 258 8 , , , cord-021063-4y8m33ea 258 9 1989 1989 CD cord-021063-4y8m33ea 258 10 ; ; : cord-021063-4y8m33ea 258 11 Lapidot Lapidot NNP cord-021063-4y8m33ea 258 12 and and CC cord-021063-4y8m33ea 258 13 Loyter Loyter NNP cord-021063-4y8m33ea 258 14 , , , cord-021063-4y8m33ea 258 15 1990 1990 CD cord-021063-4y8m33ea 258 16 ) ) -RRB- cord-021063-4y8m33ea 258 17 . . . cord-021063-4y8m33ea 259 1 Once once IN cord-021063-4y8m33ea 259 2 the the DT cord-021063-4y8m33ea 259 3 DNA dna NN cord-021063-4y8m33ea 259 4 has have VBZ cord-021063-4y8m33ea 259 5 successfully successfully RB cord-021063-4y8m33ea 259 6 been be VBN cord-021063-4y8m33ea 259 7 introduced introduce VBN cord-021063-4y8m33ea 259 8 into into IN cord-021063-4y8m33ea 259 9 the the DT cord-021063-4y8m33ea 259 10 cytoplasm cytoplasm NN cord-021063-4y8m33ea 259 11 of of IN cord-021063-4y8m33ea 259 12 the the DT cord-021063-4y8m33ea 259 13 target target NN cord-021063-4y8m33ea 259 14 cell cell NN cord-021063-4y8m33ea 259 15 , , , cord-021063-4y8m33ea 259 16 the the DT cord-021063-4y8m33ea 259 17 factors factor NNS cord-021063-4y8m33ea 259 18 governing govern VBG cord-021063-4y8m33ea 259 19 expression expression NN cord-021063-4y8m33ea 259 20 are be VBP cord-021063-4y8m33ea 259 21 much much RB cord-021063-4y8m33ea 259 22 less less RBR cord-021063-4y8m33ea 259 23 well well RB cord-021063-4y8m33ea 259 24 understood understand VBN cord-021063-4y8m33ea 259 25 . . . cord-021063-4y8m33ea 260 1 However however RB cord-021063-4y8m33ea 260 2 , , , cord-021063-4y8m33ea 260 3 proteins protein NNS cord-021063-4y8m33ea 260 4 exist exist VBP cord-021063-4y8m33ea 260 5 that that WDT cord-021063-4y8m33ea 260 6 are be VBP cord-021063-4y8m33ea 260 7 karyophilic karyophilic NNP cord-021063-4y8m33ea 261 1 , , , cord-021063-4y8m33ea 261 2 that that RB cord-021063-4y8m33ea 261 3 is is RB cord-021063-4y8m33ea 261 4 , , , cord-021063-4y8m33ea 261 5 they -PRON- PRP cord-021063-4y8m33ea 261 6 are be VBP cord-021063-4y8m33ea 261 7 actively actively RB cord-021063-4y8m33ea 261 8 transported transport VBN cord-021063-4y8m33ea 261 9 into into IN cord-021063-4y8m33ea 261 10 the the DT cord-021063-4y8m33ea 261 11 nucleus nucleus NN cord-021063-4y8m33ea 261 12 . . . cord-021063-4y8m33ea 262 1 Two two CD cord-021063-4y8m33ea 262 2 such such JJ cord-021063-4y8m33ea 262 3 proteins protein NNS cord-021063-4y8m33ea 262 4 are be VBP cord-021063-4y8m33ea 262 5 the the DT cord-021063-4y8m33ea 262 6 Semliki Semliki NNP cord-021063-4y8m33ea 262 7 Forest Forest NNP cord-021063-4y8m33ea 262 8 Virus Virus NNP cord-021063-4y8m33ea 262 9 nucleocapsid nucleocapsid NN cord-021063-4y8m33ea 262 10 protein protein NN cord-021063-4y8m33ea 262 11 ( ( -LRB- cord-021063-4y8m33ea 262 12 Michel Michel NNP cord-021063-4y8m33ea 262 13 et et NNP cord-021063-4y8m33ea 262 14 al al NNP cord-021063-4y8m33ea 262 15 . . NNP cord-021063-4y8m33ea 262 16 , , , cord-021063-4y8m33ea 262 17 1990 1990 CD cord-021063-4y8m33ea 262 18 ) ) -RRB- cord-021063-4y8m33ea 262 19 and and CC cord-021063-4y8m33ea 262 20 the the DT cord-021063-4y8m33ea 262 21 non non JJ cord-021063-4y8m33ea 262 22 - - JJ cord-021063-4y8m33ea 262 23 histone histone JJ cord-021063-4y8m33ea 262 24 high high JJ cord-021063-4y8m33ea 262 25 mobility mobility NN cord-021063-4y8m33ea 262 26 group group NN cord-021063-4y8m33ea 262 27 I -PRON- PRP cord-021063-4y8m33ea 262 28 chromosomal chromosomal JJ cord-021063-4y8m33ea 262 29 protein protein NN cord-021063-4y8m33ea 262 30 ( ( -LRB- cord-021063-4y8m33ea 262 31 HMG HMG NNP cord-021063-4y8m33ea 262 32 I I NNP cord-021063-4y8m33ea 262 33 ) ) -RRB- cord-021063-4y8m33ea 262 34 ( ( -LRB- cord-021063-4y8m33ea 262 35 Kato Kato NNP cord-021063-4y8m33ea 262 36 et et NNP cord-021063-4y8m33ea 262 37 al al NNP cord-021063-4y8m33ea 262 38 . . NNP cord-021063-4y8m33ea 262 39 , , , cord-021063-4y8m33ea 262 40 1991 1991 CD cord-021063-4y8m33ea 262 41 ; ; : cord-021063-4y8m33ea 262 42 Tomita Tomita NNP cord-021063-4y8m33ea 262 43 et et NNP cord-021063-4y8m33ea 262 44 al al NNP cord-021063-4y8m33ea 262 45 . . NNP cord-021063-4y8m33ea 262 46 , , , cord-021063-4y8m33ea 262 47 1992 1992 CD cord-021063-4y8m33ea 262 48 ) ) -RRB- cord-021063-4y8m33ea 262 49 . . . cord-021063-4y8m33ea 263 1 If if IN cord-021063-4y8m33ea 263 2 a a DT cord-021063-4y8m33ea 263 3 gene gene NN cord-021063-4y8m33ea 263 4 is be VBZ cord-021063-4y8m33ea 263 5 coencapsulated coencapsulate VBN cord-021063-4y8m33ea 263 6 in in IN cord-021063-4y8m33ea 263 7 a a DT cord-021063-4y8m33ea 263 8 liposome liposome NN cord-021063-4y8m33ea 263 9 with with IN cord-021063-4y8m33ea 263 10 HMG HMG NNP cord-021063-4y8m33ea 263 11 I I NNP cord-021063-4y8m33ea 263 12 , , , cord-021063-4y8m33ea 263 13 expression expression NN cord-021063-4y8m33ea 263 14 increases increase VBZ cord-021063-4y8m33ea 263 15 as as RB cord-021063-4y8m33ea 263 16 much much RB cord-021063-4y8m33ea 263 17 as as IN cord-021063-4y8m33ea 263 18 10-fold 10-fold JJ cord-021063-4y8m33ea 263 19 over over IN cord-021063-4y8m33ea 263 20 the the DT cord-021063-4y8m33ea 263 21 levels level NNS cord-021063-4y8m33ea 263 22 seen see VBN cord-021063-4y8m33ea 263 23 without without IN cord-021063-4y8m33ea 263 24 the the DT cord-021063-4y8m33ea 263 25 protein protein NN cord-021063-4y8m33ea 263 26 . . . cord-021063-4y8m33ea 264 1 Delivery delivery NN cord-021063-4y8m33ea 264 2 of of IN cord-021063-4y8m33ea 264 3 DNA dna NN cord-021063-4y8m33ea 264 4 / / SYM cord-021063-4y8m33ea 264 5 protein protein NN cord-021063-4y8m33ea 264 6 complexes complex NNS cord-021063-4y8m33ea 264 7 has have VBZ cord-021063-4y8m33ea 264 8 the the DT cord-021063-4y8m33ea 264 9 potential potential NN cord-021063-4y8m33ea 264 10 for for IN cord-021063-4y8m33ea 264 11 greatly greatly RB cord-021063-4y8m33ea 264 12 increasing increase VBG cord-021063-4y8m33ea 264 13 transfection transfection NN cord-021063-4y8m33ea 264 14 efficiency efficiency NN cord-021063-4y8m33ea 264 15 , , , cord-021063-4y8m33ea 264 16 and and CC cord-021063-4y8m33ea 264 17 should should MD cord-021063-4y8m33ea 264 18 prove prove VB cord-021063-4y8m33ea 264 19 to to TO cord-021063-4y8m33ea 264 20 be be VB cord-021063-4y8m33ea 264 21 compatible compatible JJ cord-021063-4y8m33ea 264 22 with with IN cord-021063-4y8m33ea 264 23 most most JJS cord-021063-4y8m33ea 264 24 methods method NNS cord-021063-4y8m33ea 264 25 of of IN cord-021063-4y8m33ea 264 26 liposomal liposomal JJ cord-021063-4y8m33ea 264 27 preparation preparation NN cord-021063-4y8m33ea 264 28 . . . cord-021063-4y8m33ea 265 1 One one CD cord-021063-4y8m33ea 265 2 shortcoming shortcoming NN cord-021063-4y8m33ea 265 3 that that IN cord-021063-4y8m33ea 265 4 all all DT cord-021063-4y8m33ea 265 5 present present JJ cord-021063-4y8m33ea 265 6 approaches approach NNS cord-021063-4y8m33ea 265 7 to to TO cord-021063-4y8m33ea 265 8 gene gene NN cord-021063-4y8m33ea 265 9 therapy therapy NN cord-021063-4y8m33ea 265 10 share share NN cord-021063-4y8m33ea 265 11 is be VBZ cord-021063-4y8m33ea 265 12 their -PRON- PRP$ cord-021063-4y8m33ea 265 13 inability inability NN cord-021063-4y8m33ea 265 14 to to TO cord-021063-4y8m33ea 265 15 maintain maintain VB cord-021063-4y8m33ea 265 16 a a DT cord-021063-4y8m33ea 265 17 high high JJ cord-021063-4y8m33ea 265 18 level level NN cord-021063-4y8m33ea 265 19 expression expression NN cord-021063-4y8m33ea 265 20 of of IN cord-021063-4y8m33ea 265 21 the the DT cord-021063-4y8m33ea 265 22 transfected transfecte VBN cord-021063-4y8m33ea 265 23 gene gene NN cord-021063-4y8m33ea 265 24 for for IN cord-021063-4y8m33ea 265 25 long long JJ cord-021063-4y8m33ea 265 26 periods period NNS cord-021063-4y8m33ea 265 27 of of IN cord-021063-4y8m33ea 265 28 time time NN cord-021063-4y8m33ea 265 29 . . . cord-021063-4y8m33ea 266 1 For for IN cord-021063-4y8m33ea 266 2 some some DT cord-021063-4y8m33ea 266 3 applications application NNS cord-021063-4y8m33ea 266 4 , , , cord-021063-4y8m33ea 266 5 such such JJ cord-021063-4y8m33ea 266 6 as as IN cord-021063-4y8m33ea 266 7 the the DT cord-021063-4y8m33ea 266 8 activation activation NN cord-021063-4y8m33ea 266 9 of of IN cord-021063-4y8m33ea 266 10 the the DT cord-021063-4y8m33ea 266 11 immune immune JJ cord-021063-4y8m33ea 266 12 system system NN cord-021063-4y8m33ea 266 13 to to TO cord-021063-4y8m33ea 266 14 fight fight VB cord-021063-4y8m33ea 266 15 a a DT cord-021063-4y8m33ea 266 16 cancer cancer NN cord-021063-4y8m33ea 266 17 , , , cord-021063-4y8m33ea 266 18 this this DT cord-021063-4y8m33ea 266 19 will will MD cord-021063-4y8m33ea 266 20 probably probably RB cord-021063-4y8m33ea 266 21 not not RB cord-021063-4y8m33ea 266 22 be be VB cord-021063-4y8m33ea 266 23 a a DT cord-021063-4y8m33ea 266 24 problem problem NN cord-021063-4y8m33ea 266 25 . . . cord-021063-4y8m33ea 267 1 However however RB cord-021063-4y8m33ea 267 2 , , , cord-021063-4y8m33ea 267 3 to to TO cord-021063-4y8m33ea 267 4 effectively effectively RB cord-021063-4y8m33ea 267 5 cure cure VB cord-021063-4y8m33ea 267 6 many many JJ cord-021063-4y8m33ea 267 7 genetic genetic JJ cord-021063-4y8m33ea 267 8 diseases disease NNS cord-021063-4y8m33ea 267 9 , , , cord-021063-4y8m33ea 267 10 the the DT cord-021063-4y8m33ea 267 11 gene gene NN cord-021063-4y8m33ea 267 12 will will MD cord-021063-4y8m33ea 267 13 need need VB cord-021063-4y8m33ea 267 14 to to TO cord-021063-4y8m33ea 267 15 be be VB cord-021063-4y8m33ea 267 16 expressed express VBN cord-021063-4y8m33ea 267 17 at at IN cord-021063-4y8m33ea 267 18 near near IN cord-021063-4y8m33ea 267 19 normal normal JJ cord-021063-4y8m33ea 267 20 levels level NNS cord-021063-4y8m33ea 267 21 throughout throughout IN cord-021063-4y8m33ea 267 22 the the DT cord-021063-4y8m33ea 267 23 patient patient NN cord-021063-4y8m33ea 267 24 's 's POS cord-021063-4y8m33ea 267 25 life life NN cord-021063-4y8m33ea 267 26 . . . cord-021063-4y8m33ea 268 1 Successful successful JJ cord-021063-4y8m33ea 268 2 transfection transfection NN cord-021063-4y8m33ea 268 3 of of IN cord-021063-4y8m33ea 268 4 cells cell NNS cord-021063-4y8m33ea 268 5 with with IN cord-021063-4y8m33ea 268 6 some some DT cord-021063-4y8m33ea 268 7 currently currently RB cord-021063-4y8m33ea 268 8 available available JJ cord-021063-4y8m33ea 268 9 viral viral JJ cord-021063-4y8m33ea 268 10 vectors vector NNS cord-021063-4y8m33ea 268 11 may may MD cord-021063-4y8m33ea 268 12 lead lead VB cord-021063-4y8m33ea 268 13 to to IN cord-021063-4y8m33ea 268 14 expression expression NN cord-021063-4y8m33ea 268 15 of of IN cord-021063-4y8m33ea 268 16 at at IN cord-021063-4y8m33ea 268 17 least least JJS cord-021063-4y8m33ea 268 18 some some DT cord-021063-4y8m33ea 268 19 viral viral JJ cord-021063-4y8m33ea 268 20 proteins protein NNS cord-021063-4y8m33ea 268 21 , , , cord-021063-4y8m33ea 268 22 resulting result VBG cord-021063-4y8m33ea 268 23 in in IN cord-021063-4y8m33ea 268 24 the the DT cord-021063-4y8m33ea 268 25 clearance clearance NN cord-021063-4y8m33ea 268 26 of of IN cord-021063-4y8m33ea 268 27 the the DT cord-021063-4y8m33ea 268 28 cells cell NNS cord-021063-4y8m33ea 268 29 by by IN cord-021063-4y8m33ea 268 30 the the DT cord-021063-4y8m33ea 268 31 host host NN cord-021063-4y8m33ea 268 32 's 's POS cord-021063-4y8m33ea 268 33 immune immune JJ cord-021063-4y8m33ea 268 34 system system NN cord-021063-4y8m33ea 268 35 . . . cord-021063-4y8m33ea 269 1 This this DT cord-021063-4y8m33ea 269 2 process process NN cord-021063-4y8m33ea 269 3 may may MD cord-021063-4y8m33ea 269 4 be be VB cord-021063-4y8m33ea 269 5 partially partially RB cord-021063-4y8m33ea 269 6 responsible responsible JJ cord-021063-4y8m33ea 269 7 for for IN cord-021063-4y8m33ea 269 8 the the DT cord-021063-4y8m33ea 269 9 loss loss NN cord-021063-4y8m33ea 269 10 of of IN cord-021063-4y8m33ea 269 11 expression expression NN cord-021063-4y8m33ea 269 12 seen see VBN cord-021063-4y8m33ea 269 13 in in IN cord-021063-4y8m33ea 269 14 transfections transfection NNS cord-021063-4y8m33ea 269 15 with with IN cord-021063-4y8m33ea 269 16 retroviral retroviral JJ cord-021063-4y8m33ea 269 17 and and CC cord-021063-4y8m33ea 269 18 adenoviral adenoviral JJ cord-021063-4y8m33ea 269 19 vectors vector NNS cord-021063-4y8m33ea 269 20 . . . cord-021063-4y8m33ea 270 1 Another another DT cord-021063-4y8m33ea 270 2 possible possible JJ cord-021063-4y8m33ea 270 3 cause cause NN cord-021063-4y8m33ea 270 4 of of IN cord-021063-4y8m33ea 270 5 low low JJ cord-021063-4y8m33ea 270 6 levels level NNS cord-021063-4y8m33ea 270 7 of of IN cord-021063-4y8m33ea 270 8 expression expression NN cord-021063-4y8m33ea 270 9 is be VBZ cord-021063-4y8m33ea 270 10 that that IN cord-021063-4y8m33ea 270 11 length length NN cord-021063-4y8m33ea 270 12 constraints constraint NNS cord-021063-4y8m33ea 270 13 of of IN cord-021063-4y8m33ea 270 14 viral viral JJ cord-021063-4y8m33ea 270 15 vectors vector NNS cord-021063-4y8m33ea 270 16 usually usually RB cord-021063-4y8m33ea 270 17 necessitate necessitate VBP cord-021063-4y8m33ea 270 18 the the DT cord-021063-4y8m33ea 270 19 use use NN cord-021063-4y8m33ea 270 20 of of IN cord-021063-4y8m33ea 270 21 cDNA cdna NN cord-021063-4y8m33ea 270 22 copies copy NNS cord-021063-4y8m33ea 270 23 of of IN cord-021063-4y8m33ea 270 24 genes gene NNS cord-021063-4y8m33ea 270 25 . . . cord-021063-4y8m33ea 271 1 These these DT cord-021063-4y8m33ea 271 2 constructs construct NNS cord-021063-4y8m33ea 271 3 do do VBP cord-021063-4y8m33ea 271 4 not not RB cord-021063-4y8m33ea 271 5 have have VB cord-021063-4y8m33ea 271 6 introns intron NNS cord-021063-4y8m33ea 271 7 , , , cord-021063-4y8m33ea 271 8 greatly greatly RB cord-021063-4y8m33ea 271 9 reducing reduce VBG cord-021063-4y8m33ea 271 10 their -PRON- PRP$ cord-021063-4y8m33ea 271 11 length length NN cord-021063-4y8m33ea 271 12 . . . cord-021063-4y8m33ea 272 1 There there EX cord-021063-4y8m33ea 272 2 is be VBZ cord-021063-4y8m33ea 272 3 some some DT cord-021063-4y8m33ea 272 4 evidence evidence NN cord-021063-4y8m33ea 272 5 from from IN cord-021063-4y8m33ea 272 6 transgenic transgenic JJ cord-021063-4y8m33ea 272 7 mouse mouse NN cord-021063-4y8m33ea 272 8 experiments experiment NNS cord-021063-4y8m33ea 272 9 that that WDT cord-021063-4y8m33ea 272 10 expression expression NN cord-021063-4y8m33ea 272 11 of of IN cord-021063-4y8m33ea 272 12 exogenous exogenous JJ cord-021063-4y8m33ea 272 13 genes gene NNS cord-021063-4y8m33ea 272 14 is be VBZ cord-021063-4y8m33ea 272 15 higher high JJR cord-021063-4y8m33ea 272 16 when when WRB cord-021063-4y8m33ea 272 17 at at IN cord-021063-4y8m33ea 272 18 least least JJS cord-021063-4y8m33ea 272 19 some some DT cord-021063-4y8m33ea 272 20 of of IN cord-021063-4y8m33ea 272 21 the the DT cord-021063-4y8m33ea 272 22 introns intron NNS cord-021063-4y8m33ea 272 23 are be VBP cord-021063-4y8m33ea 272 24 present present JJ cord-021063-4y8m33ea 273 1 ( ( -LRB- cord-021063-4y8m33ea 273 2 Brinster Brinster NNP cord-021063-4y8m33ea 273 3 et et NNP cord-021063-4y8m33ea 273 4 al al NNP cord-021063-4y8m33ea 273 5 . . NNP cord-021063-4y8m33ea 273 6 , , , cord-021063-4y8m33ea 273 7 1988 1988 CD cord-021063-4y8m33ea 273 8 ; ; : cord-021063-4y8m33ea 273 9 Palmiter Palmiter NNP cord-021063-4y8m33ea 273 10 et et NNP cord-021063-4y8m33ea 273 11 al al NNP cord-021063-4y8m33ea 273 12 . . NNP cord-021063-4y8m33ea 273 13 , , , cord-021063-4y8m33ea 273 14 1991 1991 CD cord-021063-4y8m33ea 273 15 ) ) -RRB- cord-021063-4y8m33ea 273 16 . . . cord-021063-4y8m33ea 274 1 If if IN cord-021063-4y8m33ea 274 2 this this DT cord-021063-4y8m33ea 274 3 is be VBZ cord-021063-4y8m33ea 274 4 true true JJ cord-021063-4y8m33ea 274 5 for for IN cord-021063-4y8m33ea 274 6 genes gene NNS cord-021063-4y8m33ea 274 7 inserted insert VBN cord-021063-4y8m33ea 274 8 by by IN cord-021063-4y8m33ea 274 9 viral viral JJ cord-021063-4y8m33ea 274 10 or or CC cord-021063-4y8m33ea 274 11 liposomal liposomal JJ cord-021063-4y8m33ea 274 12 methods method NNS cord-021063-4y8m33ea 274 13 , , , cord-021063-4y8m33ea 274 14 then then RB cord-021063-4y8m33ea 274 15 it -PRON- PRP cord-021063-4y8m33ea 274 16 may may MD cord-021063-4y8m33ea 274 17 be be VB cord-021063-4y8m33ea 274 18 necessary necessary JJ cord-021063-4y8m33ea 274 19 to to TO cord-021063-4y8m33ea 274 20 include include VB cord-021063-4y8m33ea 274 21 introns intron NNS cord-021063-4y8m33ea 274 22 in in IN cord-021063-4y8m33ea 274 23 the the DT cord-021063-4y8m33ea 274 24 delivered deliver VBN cord-021063-4y8m33ea 274 25 DNA DNA NNP cord-021063-4y8m33ea 274 26 to to TO cord-021063-4y8m33ea 274 27 produce produce VB cord-021063-4y8m33ea 274 28 an an DT cord-021063-4y8m33ea 274 29 adequate adequate JJ cord-021063-4y8m33ea 274 30 therapeutic therapeutic JJ cord-021063-4y8m33ea 274 31 effect effect NN cord-021063-4y8m33ea 274 32 . . . cord-021063-4y8m33ea 275 1 Unfortunately unfortunately RB cord-021063-4y8m33ea 275 2 , , , cord-021063-4y8m33ea 275 3 increasing increase VBG cord-021063-4y8m33ea 275 4 the the DT cord-021063-4y8m33ea 275 5 size size NN cord-021063-4y8m33ea 275 6 of of IN cord-021063-4y8m33ea 275 7 the the DT cord-021063-4y8m33ea 275 8 therapeutic therapeutic JJ cord-021063-4y8m33ea 275 9 gene gene NN cord-021063-4y8m33ea 275 10 would would MD cord-021063-4y8m33ea 275 11 prevent prevent VB cord-021063-4y8m33ea 275 12 the the DT cord-021063-4y8m33ea 275 13 use use NN cord-021063-4y8m33ea 275 14 of of IN cord-021063-4y8m33ea 275 15 most most JJS cord-021063-4y8m33ea 275 16 viral viral JJ cord-021063-4y8m33ea 275 17 vectors vector NNS cord-021063-4y8m33ea 275 18 . . . cord-021063-4y8m33ea 276 1 While while IN cord-021063-4y8m33ea 276 2 all all PDT cord-021063-4y8m33ea 276 3 the the DT cord-021063-4y8m33ea 276 4 methods method NNS cord-021063-4y8m33ea 276 5 of of IN cord-021063-4y8m33ea 276 6 gene gene NN cord-021063-4y8m33ea 276 7 therapy therapy NN cord-021063-4y8m33ea 276 8 have have VBP cord-021063-4y8m33ea 276 9 specific specific JJ cord-021063-4y8m33ea 276 10 advantages advantage NNS cord-021063-4y8m33ea 276 11 , , , cord-021063-4y8m33ea 276 12 none none NN cord-021063-4y8m33ea 276 13 is be VBZ cord-021063-4y8m33ea 276 14 suitable suitable JJ cord-021063-4y8m33ea 276 15 for for IN cord-021063-4y8m33ea 276 16 all all DT cord-021063-4y8m33ea 276 17 applications application NNS cord-021063-4y8m33ea 276 18 . . . cord-021063-4y8m33ea 277 1 In in IN cord-021063-4y8m33ea 277 2 an an DT cord-021063-4y8m33ea 277 3 environment environment NN cord-021063-4y8m33ea 277 4 as as RB cord-021063-4y8m33ea 277 5 complex complex JJ cord-021063-4y8m33ea 277 6 as as IN cord-021063-4y8m33ea 277 7 a a DT cord-021063-4y8m33ea 277 8 living live VBG cord-021063-4y8m33ea 277 9 organism organism NN cord-021063-4y8m33ea 277 10 , , , cord-021063-4y8m33ea 277 11 it -PRON- PRP cord-021063-4y8m33ea 277 12 is be VBZ cord-021063-4y8m33ea 277 13 futile futile JJ cord-021063-4y8m33ea 277 14 to to TO cord-021063-4y8m33ea 277 15 hope hope VB cord-021063-4y8m33ea 277 16 that that IN cord-021063-4y8m33ea 277 17 a a DT cord-021063-4y8m33ea 277 18 single single JJ cord-021063-4y8m33ea 277 19 method method NN cord-021063-4y8m33ea 277 20 might may MD cord-021063-4y8m33ea 277 21 be be VB cord-021063-4y8m33ea 277 22 ideal ideal JJ cord-021063-4y8m33ea 277 23 in in IN cord-021063-4y8m33ea 277 24 all all DT cord-021063-4y8m33ea 277 25 situations situation NNS cord-021063-4y8m33ea 277 26 . . . cord-021063-4y8m33ea 278 1 However however RB cord-021063-4y8m33ea 278 2 , , , cord-021063-4y8m33ea 278 3 the the DT cord-021063-4y8m33ea 278 4 availability availability NN cord-021063-4y8m33ea 278 5 of of IN cord-021063-4y8m33ea 278 6 many many JJ cord-021063-4y8m33ea 278 7 methods method NNS cord-021063-4y8m33ea 278 8 greatly greatly RB cord-021063-4y8m33ea 278 9 increases increase VBZ cord-021063-4y8m33ea 278 10 the the DT cord-021063-4y8m33ea 278 11 number number NN cord-021063-4y8m33ea 278 12 and and CC cord-021063-4y8m33ea 278 13 types type NNS cord-021063-4y8m33ea 278 14 of of IN cord-021063-4y8m33ea 278 15 diseases disease NNS cord-021063-4y8m33ea 278 16 that that WDT cord-021063-4y8m33ea 278 17 can can MD cord-021063-4y8m33ea 278 18 be be VB cord-021063-4y8m33ea 278 19 treated treat VBN cord-021063-4y8m33ea 278 20 . . . cord-021063-4y8m33ea 279 1 Viruses virus NNS cord-021063-4y8m33ea 279 2 have have VBP cord-021063-4y8m33ea 279 3 evolved evolve VBN cord-021063-4y8m33ea 279 4 such such JJ cord-021063-4y8m33ea 279 5 that that IN cord-021063-4y8m33ea 279 6 they -PRON- PRP cord-021063-4y8m33ea 279 7 are be VBP cord-021063-4y8m33ea 279 8 able able JJ cord-021063-4y8m33ea 279 9 to to TO cord-021063-4y8m33ea 279 10 efficiently efficiently RB cord-021063-4y8m33ea 279 11 introduce introduce VB cord-021063-4y8m33ea 279 12 and and CC cord-021063-4y8m33ea 279 13 express express VB cord-021063-4y8m33ea 279 14 exogenous exogenous JJ cord-021063-4y8m33ea 279 15 genes gene NNS cord-021063-4y8m33ea 279 16 ( ( -LRB- cord-021063-4y8m33ea 279 17 i.e. i.e. FW cord-021063-4y8m33ea 279 18 , , , cord-021063-4y8m33ea 279 19 viral viral JJ cord-021063-4y8m33ea 279 20 genes gene NNS cord-021063-4y8m33ea 279 21 ) ) -RRB- cord-021063-4y8m33ea 279 22 in in IN cord-021063-4y8m33ea 279 23 eukaryotic eukaryotic JJ cord-021063-4y8m33ea 279 24 cells cell NNS cord-021063-4y8m33ea 279 25 . . . cord-021063-4y8m33ea 280 1 However however RB cord-021063-4y8m33ea 280 2 , , , cord-021063-4y8m33ea 280 3 it -PRON- PRP cord-021063-4y8m33ea 280 4 is be VBZ cord-021063-4y8m33ea 280 5 important important JJ cord-021063-4y8m33ea 280 6 to to TO cord-021063-4y8m33ea 280 7 remember remember VB cord-021063-4y8m33ea 280 8 that that IN cord-021063-4y8m33ea 280 9 viruses virus NNS cord-021063-4y8m33ea 280 10 have have VBP cord-021063-4y8m33ea 280 11 been be VBN cord-021063-4y8m33ea 280 12 optimized optimize VBN cord-021063-4y8m33ea 280 13 by by IN cord-021063-4y8m33ea 280 14 selective selective JJ cord-021063-4y8m33ea 280 15 pressure pressure NN cord-021063-4y8m33ea 280 16 to to TO cord-021063-4y8m33ea 280 17 meet meet VB cord-021063-4y8m33ea 280 18 criteria criterion NNS cord-021063-4y8m33ea 280 19 that that WDT cord-021063-4y8m33ea 280 20 are be VBP cord-021063-4y8m33ea 280 21 not not RB cord-021063-4y8m33ea 280 22 precisely precisely RB cord-021063-4y8m33ea 280 23 those those DT cord-021063-4y8m33ea 280 24 of of IN cord-021063-4y8m33ea 280 25 gene gene NN cord-021063-4y8m33ea 280 26 therapy therapy NN cord-021063-4y8m33ea 280 27 . . . cord-021063-4y8m33ea 281 1 In in IN cord-021063-4y8m33ea 281 2 particular particular JJ cord-021063-4y8m33ea 281 3 , , , cord-021063-4y8m33ea 281 4 most most JJS cord-021063-4y8m33ea 281 5 viruses virus NNS cord-021063-4y8m33ea 281 6 need need VBP cord-021063-4y8m33ea 281 7 to to TO cord-021063-4y8m33ea 281 8 maintain maintain VB cord-021063-4y8m33ea 281 9 high high JJ cord-021063-4y8m33ea 281 10 - - HYPH cord-021063-4y8m33ea 281 11 level level NN cord-021063-4y8m33ea 281 12 expression expression NN cord-021063-4y8m33ea 281 13 of of IN cord-021063-4y8m33ea 281 14 their -PRON- PRP$ cord-021063-4y8m33ea 281 15 proteins protein NNS cord-021063-4y8m33ea 281 16 for for IN cord-021063-4y8m33ea 281 17 only only RB cord-021063-4y8m33ea 281 18 a a DT cord-021063-4y8m33ea 281 19 short short JJ cord-021063-4y8m33ea 281 20 time time NN cord-021063-4y8m33ea 281 21 , , , cord-021063-4y8m33ea 281 22 and and CC cord-021063-4y8m33ea 281 23 need nee MD cord-021063-4y8m33ea 281 24 not not RB cord-021063-4y8m33ea 281 25 be be VB cord-021063-4y8m33ea 281 26 concerned concern VBN cord-021063-4y8m33ea 281 27 with with IN cord-021063-4y8m33ea 281 28 the the DT cord-021063-4y8m33ea 281 29 viability viability NN cord-021063-4y8m33ea 281 30 of of IN cord-021063-4y8m33ea 281 31 the the DT cord-021063-4y8m33ea 281 32 host host NN cord-021063-4y8m33ea 281 33 cell cell NN cord-021063-4y8m33ea 281 34 after after IN cord-021063-4y8m33ea 281 35 infection infection NN cord-021063-4y8m33ea 281 36 . . . cord-021063-4y8m33ea 282 1 Attempts attempt NNS cord-021063-4y8m33ea 282 2 to to TO cord-021063-4y8m33ea 282 3 modify modify VB cord-021063-4y8m33ea 282 4 a a DT cord-021063-4y8m33ea 282 5 virus virus NN cord-021063-4y8m33ea 282 6 into into IN cord-021063-4y8m33ea 282 7 a a DT cord-021063-4y8m33ea 282 8 gene gene NN cord-021063-4y8m33ea 282 9 therapy therapy NN cord-021063-4y8m33ea 282 10 vector vector NN cord-021063-4y8m33ea 282 11 will will MD cord-021063-4y8m33ea 282 12 be be VB cord-021063-4y8m33ea 282 13 hampered hamper VBN cord-021063-4y8m33ea 282 14 by by IN cord-021063-4y8m33ea 282 15 this this DT cord-021063-4y8m33ea 282 16 conflict conflict NN cord-021063-4y8m33ea 282 17 . . . cord-021063-4y8m33ea 283 1 Virus virus NN cord-021063-4y8m33ea 283 2 - - HYPH cord-021063-4y8m33ea 283 3 based base VBN cord-021063-4y8m33ea 283 4 methods method NNS cord-021063-4y8m33ea 283 5 of of IN cord-021063-4y8m33ea 283 6 gene gene NN cord-021063-4y8m33ea 283 7 therapy therapy NN cord-021063-4y8m33ea 283 8 are be VBP cord-021063-4y8m33ea 283 9 likely likely JJ cord-021063-4y8m33ea 283 10 to to TO cord-021063-4y8m33ea 283 11 be be VB cord-021063-4y8m33ea 283 12 most most RBS cord-021063-4y8m33ea 283 13 useful useful JJ cord-021063-4y8m33ea 283 14 in in IN cord-021063-4y8m33ea 283 15 applications application NNS cord-021063-4y8m33ea 283 16 that that WDT cord-021063-4y8m33ea 283 17 require require VBP cord-021063-4y8m33ea 283 18 a a DT cord-021063-4y8m33ea 283 19 burst burst NN cord-021063-4y8m33ea 283 20 of of IN cord-021063-4y8m33ea 283 21 high high JJ cord-021063-4y8m33ea 283 22 - - HYPH cord-021063-4y8m33ea 283 23 level level NN cord-021063-4y8m33ea 283 24 expression expression NN cord-021063-4y8m33ea 283 25 in in IN cord-021063-4y8m33ea 283 26 many many JJ cord-021063-4y8m33ea 283 27 of of IN cord-021063-4y8m33ea 283 28 the the DT cord-021063-4y8m33ea 283 29 patient patient NN cord-021063-4y8m33ea 283 30 's 's POS cord-021063-4y8m33ea 283 31 cells cell NNS cord-021063-4y8m33ea 283 32 , , , cord-021063-4y8m33ea 283 33 such such JJ cord-021063-4y8m33ea 283 34 as as IN cord-021063-4y8m33ea 283 35 in in IN cord-021063-4y8m33ea 283 36 cancer cancer NN cord-021063-4y8m33ea 283 37 therapy therapy NN cord-021063-4y8m33ea 283 38 . . . cord-021063-4y8m33ea 284 1 Cationic cationic JJ cord-021063-4y8m33ea 284 2 lipid lipid NN cord-021063-4y8m33ea 284 3 - - HYPH cord-021063-4y8m33ea 284 4 DNA dna NN cord-021063-4y8m33ea 284 5 complexes complex NNS cord-021063-4y8m33ea 284 6 will will MD cord-021063-4y8m33ea 284 7 never never RB cord-021063-4y8m33ea 284 8 be be VB cord-021063-4y8m33ea 284 9 as as RB cord-021063-4y8m33ea 284 10 selective selective JJ cord-021063-4y8m33ea 284 11 as as IN cord-021063-4y8m33ea 284 12 either either DT cord-021063-4y8m33ea 284 13 virus virus NN cord-021063-4y8m33ea 284 14 - - : cord-021063-4y8m33ea 284 15 or or CC cord-021063-4y8m33ea 284 16 conventional conventional JJ cord-021063-4y8m33ea 284 17 liposome liposome NN cord-021063-4y8m33ea 284 18 - - HYPH cord-021063-4y8m33ea 284 19 based base VBN cord-021063-4y8m33ea 284 20 gene gene NN cord-021063-4y8m33ea 284 21 therapy therapy NN cord-021063-4y8m33ea 284 22 . . . cord-021063-4y8m33ea 285 1 However however RB cord-021063-4y8m33ea 285 2 , , , cord-021063-4y8m33ea 285 3 they -PRON- PRP cord-021063-4y8m33ea 285 4 will will MD cord-021063-4y8m33ea 285 5 remain remain VB cord-021063-4y8m33ea 285 6 much much RB cord-021063-4y8m33ea 285 7 easier easy JJR cord-021063-4y8m33ea 285 8 to to TO cord-021063-4y8m33ea 285 9 prepare prepare VB cord-021063-4y8m33ea 285 10 and and CC cord-021063-4y8m33ea 285 11 use use VB cord-021063-4y8m33ea 285 12 . . . cord-021063-4y8m33ea 286 1 The the DT cord-021063-4y8m33ea 286 2 complexes complex NNS cord-021063-4y8m33ea 286 3 will will MD cord-021063-4y8m33ea 286 4 probably probably RB cord-021063-4y8m33ea 286 5 find find VB cord-021063-4y8m33ea 286 6 their -PRON- PRP$ cord-021063-4y8m33ea 286 7 greatest great JJS cord-021063-4y8m33ea 286 8 use use NN cord-021063-4y8m33ea 286 9 in in IN cord-021063-4y8m33ea 286 10 in in IN cord-021063-4y8m33ea 286 11 vitro vitro FW cord-021063-4y8m33ea 286 12 and and CC cord-021063-4y8m33ea 286 13 animal animal NN cord-021063-4y8m33ea 286 14 gene gene NN cord-021063-4y8m33ea 286 15 transfer transfer NN cord-021063-4y8m33ea 286 16 . . . cord-021063-4y8m33ea 287 1 Although although IN cord-021063-4y8m33ea 287 2 they -PRON- PRP cord-021063-4y8m33ea 287 3 are be VBP cord-021063-4y8m33ea 287 4 currently currently RB cord-021063-4y8m33ea 287 5 more more RBR cord-021063-4y8m33ea 287 6 widely widely RB cord-021063-4y8m33ea 287 7 used use VBN cord-021063-4y8m33ea 287 8 in in IN cord-021063-4y8m33ea 287 9 all all DT cord-021063-4y8m33ea 287 10 areas area NNS cord-021063-4y8m33ea 287 11 of of IN cord-021063-4y8m33ea 287 12 gene gene NN cord-021063-4y8m33ea 287 13 transfer transfer NN cord-021063-4y8m33ea 287 14 than than IN cord-021063-4y8m33ea 287 15 any any DT cord-021063-4y8m33ea 287 16 other other JJ cord-021063-4y8m33ea 287 17 technique technique NN cord-021063-4y8m33ea 287 18 , , , cord-021063-4y8m33ea 287 19 their -PRON- PRP$ cord-021063-4y8m33ea 287 20 lack lack NN cord-021063-4y8m33ea 287 21 of of IN cord-021063-4y8m33ea 287 22 control control NN cord-021063-4y8m33ea 287 23 and and CC cord-021063-4y8m33ea 287 24 cell cell NN cord-021063-4y8m33ea 287 25 - - HYPH cord-021063-4y8m33ea 287 26 specificity specificity NN cord-021063-4y8m33ea 287 27 will will MD cord-021063-4y8m33ea 287 28 probably probably RB cord-021063-4y8m33ea 287 29 lead lead VB cord-021063-4y8m33ea 287 30 to to IN cord-021063-4y8m33ea 287 31 their -PRON- PRP$ cord-021063-4y8m33ea 287 32 replacement replacement NN cord-021063-4y8m33ea 287 33 by by IN cord-021063-4y8m33ea 287 34 viral viral JJ cord-021063-4y8m33ea 287 35 and and CC cord-021063-4y8m33ea 287 36 liposomal liposomal JJ cord-021063-4y8m33ea 287 37 methods method NNS cord-021063-4y8m33ea 287 38 of of IN cord-021063-4y8m33ea 287 39 gene gene NN cord-021063-4y8m33ea 287 40 introduction introduction NN cord-021063-4y8m33ea 287 41 in in IN cord-021063-4y8m33ea 287 42 clinical clinical JJ cord-021063-4y8m33ea 287 43 areas area NNS cord-021063-4y8m33ea 287 44 . . . cord-021063-4y8m33ea 288 1 Liposomal Liposomal NNP cord-021063-4y8m33ea 288 2 methods method NNS cord-021063-4y8m33ea 288 3 of of IN cord-021063-4y8m33ea 288 4 gene gene NN cord-021063-4y8m33ea 288 5 therapy therapy NN cord-021063-4y8m33ea 288 6 are be VBP cord-021063-4y8m33ea 288 7 flexible flexible JJ cord-021063-4y8m33ea 288 8 , , , cord-021063-4y8m33ea 288 9 in in IN cord-021063-4y8m33ea 288 10 that that DT cord-021063-4y8m33ea 288 11 all all PDT cord-021063-4y8m33ea 288 12 the the DT cord-021063-4y8m33ea 288 13 components component NNS cord-021063-4y8m33ea 288 14 of of IN cord-021063-4y8m33ea 288 15 the the DT cord-021063-4y8m33ea 288 16 system system NN cord-021063-4y8m33ea 288 17 are be VBP cord-021063-4y8m33ea 288 18 controlled control VBN cord-021063-4y8m33ea 288 19 by by IN cord-021063-4y8m33ea 288 20 the the DT cord-021063-4y8m33ea 288 21 designers designer NNS cord-021063-4y8m33ea 288 22 . . . cord-021063-4y8m33ea 289 1 As as IN cord-021063-4y8m33ea 289 2 these these DT cord-021063-4y8m33ea 289 3 systems system NNS cord-021063-4y8m33ea 289 4 have have VBP cord-021063-4y8m33ea 289 5 become become VBN cord-021063-4y8m33ea 289 6 more more RBR cord-021063-4y8m33ea 289 7 sophisticated sophisticated JJ cord-021063-4y8m33ea 289 8 , , , cord-021063-4y8m33ea 289 9 they -PRON- PRP cord-021063-4y8m33ea 289 10 have have VBP cord-021063-4y8m33ea 289 11 begun begin VBN cord-021063-4y8m33ea 289 12 to to TO cord-021063-4y8m33ea 289 13 take take VB cord-021063-4y8m33ea 289 14 on on RP cord-021063-4y8m33ea 289 15 several several JJ cord-021063-4y8m33ea 289 16 characteristics characteristic NNS cord-021063-4y8m33ea 289 17 of of IN cord-021063-4y8m33ea 289 18 the the DT cord-021063-4y8m33ea 289 19 viruses virus NNS cord-021063-4y8m33ea 289 20 that that WDT cord-021063-4y8m33ea 289 21 they -PRON- PRP cord-021063-4y8m33ea 289 22 are be VBP cord-021063-4y8m33ea 289 23 intended intend VBN cord-021063-4y8m33ea 289 24 to to TO cord-021063-4y8m33ea 289 25 replace replace VB cord-021063-4y8m33ea 289 26 . . . cord-021063-4y8m33ea 290 1 The the DT cord-021063-4y8m33ea 290 2 use use NN cord-021063-4y8m33ea 290 3 of of IN cord-021063-4y8m33ea 290 4 basic basic JJ cord-021063-4y8m33ea 290 5 substances substance NNS cord-021063-4y8m33ea 290 6 to to TO cord-021063-4y8m33ea 290 7 condense condense VB cord-021063-4y8m33ea 290 8 the the DT cord-021063-4y8m33ea 290 9 DNA dna NN cord-021063-4y8m33ea 290 10 has have VBZ cord-021063-4y8m33ea 290 11 increased increase VBN cord-021063-4y8m33ea 290 12 the the DT cord-021063-4y8m33ea 290 13 efficiency efficiency NN cord-021063-4y8m33ea 290 14 of of IN cord-021063-4y8m33ea 290 15 encapsulation encapsulation NN cord-021063-4y8m33ea 290 16 . . . cord-021063-4y8m33ea 291 1 The the DT cord-021063-4y8m33ea 291 2 addition addition NN cord-021063-4y8m33ea 291 3 of of IN cord-021063-4y8m33ea 291 4 nucleophilic nucleophilic JJ cord-021063-4y8m33ea 291 5 proteins protein NNS cord-021063-4y8m33ea 291 6 raises raise VBZ cord-021063-4y8m33ea 291 7 the the DT cord-021063-4y8m33ea 291 8 efficiency efficiency NN cord-021063-4y8m33ea 291 9 of of IN cord-021063-4y8m33ea 291 10 transfection transfection NN cord-021063-4y8m33ea 291 11 . . . cord-021063-4y8m33ea 292 1 By by IN cord-021063-4y8m33ea 292 2 adding add VBG cord-021063-4y8m33ea 292 3 antibodies antibody NNS cord-021063-4y8m33ea 292 4 or or CC cord-021063-4y8m33ea 292 5 other other JJ cord-021063-4y8m33ea 292 6 targeting target VBG cord-021063-4y8m33ea 292 7 molecules molecule NNS cord-021063-4y8m33ea 292 8 to to IN cord-021063-4y8m33ea 292 9 the the DT cord-021063-4y8m33ea 292 10 surface surface NN cord-021063-4y8m33ea 292 11 of of IN cord-021063-4y8m33ea 292 12 liposomes liposome NNS cord-021063-4y8m33ea 292 13 , , , cord-021063-4y8m33ea 292 14 preferential preferential JJ cord-021063-4y8m33ea 292 15 binding binding NN cord-021063-4y8m33ea 292 16 of of IN cord-021063-4y8m33ea 292 17 vesicles vesicle NNS cord-021063-4y8m33ea 292 18 to to IN cord-021063-4y8m33ea 292 19 a a DT cord-021063-4y8m33ea 292 20 desired desire VBN cord-021063-4y8m33ea 292 21 cell cell NN cord-021063-4y8m33ea 292 22 type type NN cord-021063-4y8m33ea 292 23 has have VBZ cord-021063-4y8m33ea 292 24 been be VBN cord-021063-4y8m33ea 292 25 increased increase VBN cord-021063-4y8m33ea 292 26 . . . cord-021063-4y8m33ea 293 1 The the DT cord-021063-4y8m33ea 293 2 incorporation incorporation NN cord-021063-4y8m33ea 293 3 of of IN cord-021063-4y8m33ea 293 4 viral viral JJ cord-021063-4y8m33ea 293 5 fusion fusion NN cord-021063-4y8m33ea 293 6 proteins protein NNS cord-021063-4y8m33ea 293 7 into into IN cord-021063-4y8m33ea 293 8 the the DT cord-021063-4y8m33ea 293 9 membrane membrane NN cord-021063-4y8m33ea 293 10 allows allow VBZ cord-021063-4y8m33ea 293 11 a a DT cord-021063-4y8m33ea 293 12 greater great JJR cord-021063-4y8m33ea 293 13 fraction fraction NN cord-021063-4y8m33ea 293 14 of of IN cord-021063-4y8m33ea 293 15 liposomes liposome NNS cord-021063-4y8m33ea 293 16 binding bind VBG cord-021063-4y8m33ea 293 17 to to IN cord-021063-4y8m33ea 293 18 cells cell NNS cord-021063-4y8m33ea 293 19 to to TO cord-021063-4y8m33ea 293 20 deliver deliver VB cord-021063-4y8m33ea 293 21 their -PRON- PRP$ cord-021063-4y8m33ea 293 22 contents content NNS cord-021063-4y8m33ea 293 23 into into IN cord-021063-4y8m33ea 293 24 the the DT cord-021063-4y8m33ea 293 25 cytoplasm cytoplasm NN cord-021063-4y8m33ea 293 26 . . . cord-021063-4y8m33ea 294 1 In in IN cord-021063-4y8m33ea 294 2 short short JJ cord-021063-4y8m33ea 294 3 , , , cord-021063-4y8m33ea 294 4 many many JJ cord-021063-4y8m33ea 294 5 aspects aspect NNS cord-021063-4y8m33ea 294 6 of of IN cord-021063-4y8m33ea 294 7 a a DT cord-021063-4y8m33ea 294 8 virus virus NN cord-021063-4y8m33ea 294 9 from from IN cord-021063-4y8m33ea 294 10 budding bud VBG cord-021063-4y8m33ea 294 11 to to IN cord-021063-4y8m33ea 294 12 delivery delivery NN cord-021063-4y8m33ea 294 13 of of IN cord-021063-4y8m33ea 294 14 the the DT cord-021063-4y8m33ea 294 15 genetic genetic JJ cord-021063-4y8m33ea 294 16 material material NN cord-021063-4y8m33ea 294 17 to to IN cord-021063-4y8m33ea 294 18 the the DT cord-021063-4y8m33ea 294 19 nucleus nucleus NN cord-021063-4y8m33ea 294 20 have have VBP cord-021063-4y8m33ea 294 21 been be VBN cord-021063-4y8m33ea 294 22 mimicked mimic VBN cord-021063-4y8m33ea 294 23 in in IN cord-021063-4y8m33ea 294 24 liposomal liposomal JJ cord-021063-4y8m33ea 294 25 vectors vector NNS cord-021063-4y8m33ea 294 26 . . . cord-021063-4y8m33ea 295 1 Current current JJ cord-021063-4y8m33ea 295 2 methods method NNS cord-021063-4y8m33ea 295 3 of of IN cord-021063-4y8m33ea 295 4 liposome liposome NN cord-021063-4y8m33ea 295 5 - - HYPH cord-021063-4y8m33ea 295 6 based base VBN cord-021063-4y8m33ea 295 7 gene gene NN cord-021063-4y8m33ea 295 8 therapy therapy NN cord-021063-4y8m33ea 295 9 may may MD cord-021063-4y8m33ea 295 10 be be VB cord-021063-4y8m33ea 295 11 improved improve VBN cord-021063-4y8m33ea 295 12 by by IN cord-021063-4y8m33ea 295 13 modifying modify VBG cord-021063-4y8m33ea 295 14 the the DT cord-021063-4y8m33ea 295 15 structure structure NN cord-021063-4y8m33ea 295 16 of of IN cord-021063-4y8m33ea 295 17 the the DT cord-021063-4y8m33ea 295 18 introduced introduce VBN cord-021063-4y8m33ea 295 19 gene gene NN cord-021063-4y8m33ea 295 20 . . . cord-021063-4y8m33ea 296 1 Here here RB cord-021063-4y8m33ea 296 2 , , , cord-021063-4y8m33ea 296 3 preliminary preliminary JJ cord-021063-4y8m33ea 296 4 indications indication NNS cord-021063-4y8m33ea 296 5 are be VBP cord-021063-4y8m33ea 296 6 that that IN cord-021063-4y8m33ea 296 7 constructs construct NNS cord-021063-4y8m33ea 296 8 resembling resemble VBG cord-021063-4y8m33ea 296 9 native native JJ cord-021063-4y8m33ea 296 10 genes gene NNS cord-021063-4y8m33ea 296 11 , , , cord-021063-4y8m33ea 296 12 rather rather RB cord-021063-4y8m33ea 296 13 than than IN cord-021063-4y8m33ea 296 14 cDNAs cdna NNS cord-021063-4y8m33ea 296 15 , , , cord-021063-4y8m33ea 296 16 will will MD cord-021063-4y8m33ea 296 17 provide provide VB cord-021063-4y8m33ea 296 18 the the DT cord-021063-4y8m33ea 296 19 best good JJS cord-021063-4y8m33ea 296 20 long long JJ cord-021063-4y8m33ea 296 21 - - HYPH cord-021063-4y8m33ea 296 22 term term NN cord-021063-4y8m33ea 296 23 expression expression NN cord-021063-4y8m33ea 296 24 . . . cord-021063-4y8m33ea 297 1 Not not RB cord-021063-4y8m33ea 297 2 all all PDT cord-021063-4y8m33ea 297 3 these these DT cord-021063-4y8m33ea 297 4 enhancements enhancement NNS cord-021063-4y8m33ea 297 5 to to IN cord-021063-4y8m33ea 297 6 the the DT cord-021063-4y8m33ea 297 7 basic basic JJ cord-021063-4y8m33ea 297 8 liposome liposome NN cord-021063-4y8m33ea 297 9 have have VBP cord-021063-4y8m33ea 297 10 been be VBN cord-021063-4y8m33ea 297 11 used use VBN cord-021063-4y8m33ea 297 12 together together RB cord-021063-4y8m33ea 297 13 , , , cord-021063-4y8m33ea 297 14 and and CC cord-021063-4y8m33ea 297 15 not not RB cord-021063-4y8m33ea 297 16 all all DT cord-021063-4y8m33ea 297 17 of of IN cord-021063-4y8m33ea 297 18 them -PRON- PRP cord-021063-4y8m33ea 297 19 are be VBP cord-021063-4y8m33ea 297 20 mutually mutually RB cord-021063-4y8m33ea 297 21 compatible compatible JJ cord-021063-4y8m33ea 297 22 . . . cord-021063-4y8m33ea 298 1 However however RB cord-021063-4y8m33ea 298 2 , , , cord-021063-4y8m33ea 298 3 it -PRON- PRP cord-021063-4y8m33ea 298 4 seems seem VBZ cord-021063-4y8m33ea 298 5 inevitable inevitable JJ cord-021063-4y8m33ea 298 6 that that IN cord-021063-4y8m33ea 298 7 the the DT cord-021063-4y8m33ea 298 8 best good JJS cord-021063-4y8m33ea 298 9 liposome liposome NN cord-021063-4y8m33ea 298 10 - - HYPH cord-021063-4y8m33ea 298 11 based base VBN cord-021063-4y8m33ea 298 12 gene gene NN cord-021063-4y8m33ea 298 13 therapy therapy NN cord-021063-4y8m33ea 298 14 vectors vector NNS cord-021063-4y8m33ea 298 15 will will MD cord-021063-4y8m33ea 298 16 eventually eventually RB cord-021063-4y8m33ea 298 17 combine combine VB cord-021063-4y8m33ea 298 18 many many JJ cord-021063-4y8m33ea 298 19 of of IN cord-021063-4y8m33ea 298 20 these these DT cord-021063-4y8m33ea 298 21 enhancements enhancement NNS cord-021063-4y8m33ea 298 22 . . . cord-021063-4y8m33ea 299 1 The the DT cord-021063-4y8m33ea 299 2 resulting result VBG cord-021063-4y8m33ea 299 3 liposome liposome NN cord-021063-4y8m33ea 299 4 , , , cord-021063-4y8m33ea 299 5 with with IN cord-021063-4y8m33ea 299 6 a a DT cord-021063-4y8m33ea 299 7 condensed condense VBN cord-021063-4y8m33ea 299 8 DNA dna NN cord-021063-4y8m33ea 299 9 - - HYPH cord-021063-4y8m33ea 299 10 protein protein NN cord-021063-4y8m33ea 299 11 complex complex NN cord-021063-4y8m33ea 299 12 containing contain VBG cord-021063-4y8m33ea 299 13 both both DT cord-021063-4y8m33ea 299 14 histonelike histonelike JJ cord-021063-4y8m33ea 299 15 proteins protein NNS cord-021063-4y8m33ea 299 16 and and CC cord-021063-4y8m33ea 299 17 nuclear nuclear JJ cord-021063-4y8m33ea 299 18 targeting targeting NN cord-021063-4y8m33ea 299 19 proteins protein NNS cord-021063-4y8m33ea 299 20 , , , cord-021063-4y8m33ea 299 21 a a DT cord-021063-4y8m33ea 299 22 membrane membrane NN cord-021063-4y8m33ea 299 23 designed design VBN cord-021063-4y8m33ea 299 24 for for IN cord-021063-4y8m33ea 299 25 long long JJ cord-021063-4y8m33ea 299 26 circulation circulation NN cord-021063-4y8m33ea 299 27 within within IN cord-021063-4y8m33ea 299 28 the the DT cord-021063-4y8m33ea 299 29 blood blood NN cord-021063-4y8m33ea 299 30 , , , cord-021063-4y8m33ea 299 31 targeting target VBG cord-021063-4y8m33ea 299 32 molecules molecule NNS cord-021063-4y8m33ea 299 33 on on IN cord-021063-4y8m33ea 299 34 the the DT cord-021063-4y8m33ea 299 35 surface surface NN cord-021063-4y8m33ea 299 36 , , , cord-021063-4y8m33ea 299 37 and and CC cord-021063-4y8m33ea 299 38 viral viral JJ cord-021063-4y8m33ea 299 39 fusion fusion NN cord-021063-4y8m33ea 299 40 proteins protein NNS cord-021063-4y8m33ea 299 41 in in IN cord-021063-4y8m33ea 299 42 the the DT cord-021063-4y8m33ea 299 43 membrane membrane NN cord-021063-4y8m33ea 299 44 , , , cord-021063-4y8m33ea 299 45 will will MD cord-021063-4y8m33ea 299 46 in in IN cord-021063-4y8m33ea 299 47 effect effect NN cord-021063-4y8m33ea 299 48 be be VB cord-021063-4y8m33ea 299 49 a a DT cord-021063-4y8m33ea 299 50 completely completely RB cord-021063-4y8m33ea 299 51 man man NN cord-021063-4y8m33ea 299 52 - - HYPH cord-021063-4y8m33ea 299 53 made make VBN cord-021063-4y8m33ea 299 54 nonreplicative nonreplicative NNP cord-021063-4y8m33ea 299 55 virus virus NN cord-021063-4y8m33ea 299 56 . . . cord-021063-4y8m33ea 299 57 _SP cord-021063-4y8m33ea 300 1 Liposomes liposome VBN cord-021063-4y8m33ea 300 2 with with IN cord-021063-4y8m33ea 300 3 prolonged prolonged JJ cord-021063-4y8m33ea 300 4 circulation circulation NN cord-021063-4y8m33ea 300 5 times time NNS cord-021063-4y8m33ea 300 6 : : : cord-021063-4y8m33ea 300 7 factors factor NNS cord-021063-4y8m33ea 300 8 affecting affect VBG cord-021063-4y8m33ea 300 9 uptake uptake NN cord-021063-4y8m33ea 300 10 by by IN cord-021063-4y8m33ea 300 11 reticuloendothelial reticuloendothelial JJ cord-021063-4y8m33ea 300 12 and and CC cord-021063-4y8m33ea 300 13 other other JJ cord-021063-4y8m33ea 300 14 tissues tissue NNS cord-021063-4y8m33ea 301 1 Molecular molecular JJ cord-021063-4y8m33ea 301 2 mechanism mechanism NN cord-021063-4y8m33ea 301 3 of of IN cord-021063-4y8m33ea 301 4 the the DT cord-021063-4y8m33ea 301 5 lipid lipid NN cord-021063-4y8m33ea 301 6 vesicle vesicle NN cord-021063-4y8m33ea 301 7 longevity longevity NN cord-021063-4y8m33ea 301 8 in in IN cord-021063-4y8m33ea 301 9 vivo vivo NNP cord-021063-4y8m33ea 301 10 Expression expression NN cord-021063-4y8m33ea 301 11 of of IN cord-021063-4y8m33ea 301 12 human human JJ cord-021063-4y8m33ea 301 13 growth growth NN cord-021063-4y8m33ea 301 14 hormone hormone NN cord-021063-4y8m33ea 301 15 fusion fusion NN cord-021063-4y8m33ea 301 16 genes gene NNS cord-021063-4y8m33ea 301 17 in in IN cord-021063-4y8m33ea 301 18 cultured cultured JJ cord-021063-4y8m33ea 301 19 lung lung NN cord-021063-4y8m33ea 301 20 endothelial endothelial NN cord-021063-4y8m33ea 301 21 cells cell NNS cord-021063-4y8m33ea 301 22 and and CC cord-021063-4y8m33ea 301 23 in in IN cord-021063-4y8m33ea 301 24 the the DT cord-021063-4y8m33ea 301 25 lungs lung NNS cord-021063-4y8m33ea 301 26 of of IN cord-021063-4y8m33ea 301 27 mice mice NN cord-021063-4y8m33ea 301 28 lntrons lntron NNS cord-021063-4y8m33ea 301 29 increase increase VBP cord-021063-4y8m33ea 301 30 transcriptional transcriptional JJ cord-021063-4y8m33ea 301 31 efficiency efficiency NN cord-021063-4y8m33ea 301 32 in in IN cord-021063-4y8m33ea 301 33 transgenic transgenic JJ cord-021063-4y8m33ea 301 34 mice mouse NNS cord-021063-4y8m33ea 301 35 Modulation modulation NN cord-021063-4y8m33ea 301 36 of of IN cord-021063-4y8m33ea 301 37 coronavirus coronavirus NN cord-021063-4y8m33ea 301 38 - - HYPH cord-021063-4y8m33ea 301 39 mediated mediate VBN cord-021063-4y8m33ea 301 40 cell cell NN cord-021063-4y8m33ea 301 41 fusion fusion NN cord-021063-4y8m33ea 301 42 by by IN cord-021063-4y8m33ea 301 43 homeostatic homeostatic JJ cord-021063-4y8m33ea 301 44 control control NN cord-021063-4y8m33ea 301 45 of of IN cord-021063-4y8m33ea 301 46 cholesterol cholesterol NN cord-021063-4y8m33ea 301 47 and and CC cord-021063-4y8m33ea 301 48 fatty fatty JJ cord-021063-4y8m33ea 301 49 acid acid NN cord-021063-4y8m33ea 301 50 metabolism metabolism NN cord-021063-4y8m33ea 301 51 Gene Gene NNP cord-021063-4y8m33ea 301 52 therapy therapy NN cord-021063-4y8m33ea 301 53 strategies strategy NNS cord-021063-4y8m33ea 301 54 for for IN cord-021063-4y8m33ea 301 55 pulmonary pulmonary JJ cord-021063-4y8m33ea 301 56 disease disease NN cord-021063-4y8m33ea 301 57 19q_'2 19q_'2 NNP cord-021063-4y8m33ea 301 58 ) ) -RRB- cord-021063-4y8m33ea 301 59 Effect effect NN cord-021063-4y8m33ea 301 60 of of IN cord-021063-4y8m33ea 301 61 cationic cationic JJ cord-021063-4y8m33ea 301 62 cho!e cho!e JJ cord-021063-4y8m33ea 302 1 ~terol ~terol NFP cord-021063-4y8m33ea 302 2 derivatives derivative NNS cord-021063-4y8m33ea 302 3 on on IN cord-021063-4y8m33ea 302 4 gene gene NN cord-021063-4y8m33ea 302 5 transfer transfer NN cord-021063-4y8m33ea 302 6 and and CC cord-021063-4y8m33ea 302 7 protein protein NN cord-021063-4y8m33ea 302 8 kinase kinase NN cord-021063-4y8m33ea 302 9 C c NN cord-021063-4y8m33ea 302 10 activity activity NN cord-021063-4y8m33ea 302 11 Introduction introduction NN cord-021063-4y8m33ea 302 12 of of IN cord-021063-4y8m33ea 302 13 liposome liposome NN cord-021063-4y8m33ea 302 14 - - HYPH cord-021063-4y8m33ea 302 15 encapsulated encapsulate VBN cord-021063-4y8m33ea 302 16 SV40 SV40 NNP cord-021063-4y8m33ea 302 17 DNA DNA NNP cord-021063-4y8m33ea 302 18 into into IN cord-021063-4y8m33ea 302 19 cells cell NNS cord-021063-4y8m33ea 303 1 The the DT cord-021063-4y8m33ea 303 2 role role NN cord-021063-4y8m33ea 303 3 of of IN cord-021063-4y8m33ea 303 4 surface surface NN cord-021063-4y8m33ea 303 5 charge charge NN cord-021063-4y8m33ea 303 6 and and CC cord-021063-4y8m33ea 303 7 hydrophilic hydrophilic JJ cord-021063-4y8m33ea 303 8 groups group NNS cord-021063-4y8m33ea 303 9 on on IN cord-021063-4y8m33ea 303 10 liposome liposome NN cord-021063-4y8m33ea 303 11 clearance clearance NN cord-021063-4y8m33ea 303 12 in in IN cord-021063-4y8m33ea 303 13 vivo vivo NNP cord-021063-4y8m33ea 303 14 A a DT cord-021063-4y8m33ea 303 15 novel novel JJ cord-021063-4y8m33ea 303 16 cationic cationic JJ cord-021063-4y8m33ea 303 17 liposome liposome NN cord-021063-4y8m33ea 303 18 reagent reagent NN cord-021063-4y8m33ea 303 19 for for IN cord-021063-4y8m33ea 303 20 efficient efficient JJ cord-021063-4y8m33ea 303 21 transfection transfection NN cord-021063-4y8m33ea 303 22 of of IN cord-021063-4y8m33ea 303 23 mammalian mammalian JJ cord-021063-4y8m33ea 303 24 cells cell NNS cord-021063-4y8m33ea 303 25 Herpesviruses Herpesviruses NNP cord-021063-4y8m33ea 303 26 : : : cord-021063-4y8m33ea 303 27 expression expression NN cord-021063-4y8m33ea 303 28 of of IN cord-021063-4y8m33ea 303 29 genes gene NNS cord-021063-4y8m33ea 303 30 in in IN cord-021063-4y8m33ea 303 31 postmitotic postmitotic JJ cord-021063-4y8m33ea 303 32 brain brain NN cord-021063-4y8m33ea 303 33 cells cell NNS cord-021063-4y8m33ea 303 34 Chimerasome Chimerasome NNP cord-021063-4y8m33ea 303 35 - - HYPH cord-021063-4y8m33ea 303 36 mediated mediate VBN cord-021063-4y8m33ea 303 37 gene gene NN cord-021063-4y8m33ea 303 38 transfer transfer NN cord-021063-4y8m33ea 303 39 in in IN cord-021063-4y8m33ea 303 40 vitro vitro FW cord-021063-4y8m33ea 303 41 and and CC cord-021063-4y8m33ea 303 42 in in IN cord-021063-4y8m33ea 303 43 vivo vivo NNP cord-021063-4y8m33ea 303 44 Flow Flow NNP cord-021063-4y8m33ea 303 45 cytofluorometric cytofluorometric JJ cord-021063-4y8m33ea 303 46 investigation investigation NN cord-021063-4y8m33ea 303 47 of of IN cord-021063-4y8m33ea 303 48 the the DT cord-021063-4y8m33ea 303 49 uptake uptake NN cord-021063-4y8m33ea 303 50 by by IN cord-021063-4y8m33ea 303 51 hepatocytes hepatocyte NNS cord-021063-4y8m33ea 303 52 and and CC cord-021063-4y8m33ea 303 53 spleen spleen NN cord-021063-4y8m33ea 303 54 cells cell NNS cord-021063-4y8m33ea 303 55 of of IN cord-021063-4y8m33ea 303 56 targeted target VBN cord-021063-4y8m33ea 303 57 and and CC cord-021063-4y8m33ea 303 58 untargeted untargeted JJ cord-021063-4y8m33ea 303 59 liposomes liposome NNS cord-021063-4y8m33ea 303 60 injected inject VBN cord-021063-4y8m33ea 303 61 intravenously intravenously RB cord-021063-4y8m33ea 303 62 into into IN cord-021063-4y8m33ea 303 63 mice mouse NNS cord-021063-4y8m33ea 303 64 Localization localization NN cord-021063-4y8m33ea 303 65 and and CC cord-021063-4y8m33ea 303 66 induced induce VBN cord-021063-4y8m33ea 303 67 expression expression NN cord-021063-4y8m33ea 303 68 of of IN cord-021063-4y8m33ea 303 69 fusion fusion NN cord-021063-4y8m33ea 303 70 genes gene NNS cord-021063-4y8m33ea 303 71 in in IN cord-021063-4y8m33ea 303 72 the the DT cord-021063-4y8m33ea 303 73 rat rat NN cord-021063-4y8m33ea 303 74 lung lung NN cord-021063-4y8m33ea 303 75 Gene Gene NNP cord-021063-4y8m33ea 303 76 therapy therapy NN cord-021063-4y8m33ea 303 77 for for IN cord-021063-4y8m33ea 303 78 human human JJ cord-021063-4y8m33ea 303 79 inherited inherit VBN cord-021063-4y8m33ea 303 80 disorders disorder NNS cord-021063-4y8m33ea 303 81 : : : cord-021063-4y8m33ea 303 82 techniques technique NNS cord-021063-4y8m33ea 303 83 and and CC cord-021063-4y8m33ea 303 84 status status NN cord-021063-4y8m33ea 303 85 Treatment treatment NN cord-021063-4y8m33ea 303 86 of of IN cord-021063-4y8m33ea 303 87 patients patient NNS cord-021063-4y8m33ea 303 88 with with IN cord-021063-4y8m33ea 303 89 severe severe JJ cord-021063-4y8m33ea 303 90 combined combine VBN cord-021063-4y8m33ea 303 91 immunodeficiency immunodeficiency NN cord-021063-4y8m33ea 303 92 due due IN cord-021063-4y8m33ea 303 93 to to IN cord-021063-4y8m33ea 304 1 adenosine adenosine NN cord-021063-4y8m33ea 304 2 deaminase deaminase NNP cord-021063-4y8m33ea 304 3 ( ( -LRB- cord-021063-4y8m33ea 304 4 ADA ADA NNP cord-021063-4y8m33ea 304 5 ) ) -RRB- cord-021063-4y8m33ea 304 6 deficiency deficiency NN cord-021063-4y8m33ea 304 7 by by IN cord-021063-4y8m33ea 304 8 autologous autologous JJ cord-021063-4y8m33ea 304 9 transplantation transplantation NN cord-021063-4y8m33ea 304 10 of of IN cord-021063-4y8m33ea 304 11 genetically genetically RB cord-021063-4y8m33ea 304 12 modified modify VBN cord-021063-4y8m33ea 304 13 bone bone NN cord-021063-4y8m33ea 304 14 marrow marrow NN cord-021063-4y8m33ea 304 15 cells cell NNS cord-021063-4y8m33ea 304 16 Liposome liposome NN cord-021063-4y8m33ea 304 17 - - HYPH cord-021063-4y8m33ea 304 18 mediated mediate VBN cord-021063-4y8m33ea 304 19 transformation transformation NN cord-021063-4y8m33ea 304 20 of of IN cord-021063-4y8m33ea 304 21 eukaryotic eukaryotic JJ cord-021063-4y8m33ea 304 22 cells cell NNS cord-021063-4y8m33ea 304 23 Synthetic synthetic JJ cord-021063-4y8m33ea 304 24 cationic cationic JJ cord-021063-4y8m33ea 304 25 amphiphiles amphiphile NNS cord-021063-4y8m33ea 304 26 for for IN cord-021063-4y8m33ea 304 27 liposome liposome NN cord-021063-4y8m33ea 304 28 - - HYPH cord-021063-4y8m33ea 304 29 mediated mediate VBN cord-021063-4y8m33ea 304 30 DNA dna NN cord-021063-4y8m33ea 304 31 transfection transfection NN cord-021063-4y8m33ea 304 32 Basic basic JJ cord-021063-4y8m33ea 304 33 protein protein NN cord-021063-4y8m33ea 304 34 enhances enhance VBZ cord-021063-4y8m33ea 304 35 the the DT cord-021063-4y8m33ea 304 36 incorporation incorporation NN cord-021063-4y8m33ea 304 37 of of IN cord-021063-4y8m33ea 304 38 DNA DNA NNP cord-021063-4y8m33ea 304 39 into into IN cord-021063-4y8m33ea 304 40 lipid lipid NN cord-021063-4y8m33ea 304 41 vesicles vesicle NNS cord-021063-4y8m33ea 304 42 : : : cord-021063-4y8m33ea 304 43 model model NN cord-021063-4y8m33ea 304 44 for for IN cord-021063-4y8m33ea 304 45 the the DT cord-021063-4y8m33ea 304 46 formation formation NN cord-021063-4y8m33ea 304 47 of of IN cord-021063-4y8m33ea 304 48 primordial primordial JJ cord-021063-4y8m33ea 304 49 cells cell NNS cord-021063-4y8m33ea 304 50 Experimental experimental JJ cord-021063-4y8m33ea 304 51 models model NNS cord-021063-4y8m33ea 304 52 of of IN cord-021063-4y8m33ea 304 53 altering alter VBG cord-021063-4y8m33ea 304 54 the the DT cord-021063-4y8m33ea 304 55 blood blood NN cord-021063-4y8m33ea 304 56 - - HYPH cord-021063-4y8m33ea 304 57 brain brain NN cord-021063-4y8m33ea 304 58 barrier barrier NN cord-021063-4y8m33ea 304 59 Direct direct JJ cord-021063-4y8m33ea 304 60 injection injection NN cord-021063-4y8m33ea 304 61 of of IN cord-021063-4y8m33ea 304 62 hepatitis hepatitis NN cord-021063-4y8m33ea 304 63 B B NNP cord-021063-4y8m33ea 304 64 virus virus NN cord-021063-4y8m33ea 304 65 DNA dna NN cord-021063-4y8m33ea 304 66 into into IN cord-021063-4y8m33ea 304 67 liver liver NN cord-021063-4y8m33ea 304 68 induced induce VBN cord-021063-4y8m33ea 304 69 hepatitis hepatitis NN cord-021063-4y8m33ea 304 70 in in IN cord-021063-4y8m33ea 304 71 adult adult NN cord-021063-4y8m33ea 304 72 rats rat NNS cord-021063-4y8m33ea 304 73 Activity Activity NNP cord-021063-4y8m33ea 304 74 of of IN cord-021063-4y8m33ea 304 75 amphipathic amphipathic NNP cord-021063-4y8m33ea 304 76 poly(ethylene poly(ethylene NNP cord-021063-4y8m33ea 304 77 glycol glycol NN cord-021063-4y8m33ea 304 78 ) ) -RRB- cord-021063-4y8m33ea 304 79 5000 5000 CD cord-021063-4y8m33ea 304 80 to to TO cord-021063-4y8m33ea 304 81 prolong prolong VB cord-021063-4y8m33ea 304 82 the the DT cord-021063-4y8m33ea 304 83 circulation circulation NN cord-021063-4y8m33ea 304 84 time time NN cord-021063-4y8m33ea 304 85 of of IN cord-021063-4y8m33ea 304 86 liposomes liposome NNS cord-021063-4y8m33ea 304 87 depends depend VBZ cord-021063-4y8m33ea 304 88 on on IN cord-021063-4y8m33ea 304 89 the the DT cord-021063-4y8m33ea 304 90 liposome liposome NN cord-021063-4y8m33ea 304 91 size size NN cord-021063-4y8m33ea 304 92 and and CC cord-021063-4y8m33ea 304 93 is be VBZ cord-021063-4y8m33ea 304 94 unfavorable unfavorable JJ cord-021063-4y8m33ea 304 95 for for IN cord-021063-4y8m33ea 304 96 immunoliposome immunoliposome NN cord-021063-4y8m33ea 304 97 binding bind VBG cord-021063-4y8m33ea 304 98 to to TO cord-021063-4y8m33ea 304 99 target target VB cord-021063-4y8m33ea 304 100 Gene Gene NNP cord-021063-4y8m33ea 304 101 therapy therapy NN cord-021063-4y8m33ea 304 102 : : : cord-021063-4y8m33ea 304 103 Adenovirus Adenovirus NNP cord-021063-4y8m33ea 304 104 vectors vector NNS cord-021063-4y8m33ea 304 105 Fusion fusion NN cord-021063-4y8m33ea 304 106 - - HYPH cord-021063-4y8m33ea 304 107 mediated mediate VBN cord-021063-4y8m33ea 304 108 microinjection microinjection NN cord-021063-4y8m33ea 304 109 of of IN cord-021063-4y8m33ea 304 110 liposome liposome NN cord-021063-4y8m33ea 304 111 - - HYPH cord-021063-4y8m33ea 304 112 enclosed enclose VBN cord-021063-4y8m33ea 304 113 DNA dna NN cord-021063-4y8m33ea 304 114 into into IN cord-021063-4y8m33ea 304 115 cultured cultured JJ cord-021063-4y8m33ea 304 116 cells cell NNS cord-021063-4y8m33ea 304 117 with with IN cord-021063-4y8m33ea 304 118 the the DT cord-021063-4y8m33ea 304 119 aid aid NN cord-021063-4y8m33ea 304 120 of of IN cord-021063-4y8m33ea 304 121 influenza influenza NN cord-021063-4y8m33ea 304 122 virus virus NN cord-021063-4y8m33ea 304 123 glycoproteins glycoprotein NNS cord-021063-4y8m33ea 304 124 Sterically sterically RB cord-021063-4y8m33ea 304 125 stabilized stabilize VBD cord-021063-4y8m33ea 304 126 liposomes liposome NNS cord-021063-4y8m33ea 304 127 : : : cord-021063-4y8m33ea 305 1 A a DT cord-021063-4y8m33ea 305 2 hypothesis hypothesis NN cord-021063-4y8m33ea 305 3 on on IN cord-021063-4y8m33ea 305 4 the the DT cord-021063-4y8m33ea 305 5 molecular molecular JJ cord-021063-4y8m33ea 305 6 origin origin NN cord-021063-4y8m33ea 305 7 of of IN cord-021063-4y8m33ea 305 8 the the DT cord-021063-4y8m33ea 305 9 extended extended JJ cord-021063-4y8m33ea 305 10 circulation circulation NN cord-021063-4y8m33ea 305 11 times time NNS cord-021063-4y8m33ea 305 12 Recognition Recognition NNP cord-021063-4y8m33ea 305 13 of of IN cord-021063-4y8m33ea 305 14 liposomes liposome NNS cord-021063-4y8m33ea 305 15 by by IN cord-021063-4y8m33ea 305 16 cells cell NNS cord-021063-4y8m33ea 305 17 : : : cord-021063-4y8m33ea 305 18 In in IN cord-021063-4y8m33ea 305 19 vitro vitro FW cord-021063-4y8m33ea 305 20 binding binding NN cord-021063-4y8m33ea 305 21 and and CC cord-021063-4y8m33ea 305 22 endocytosis endocytosis NN cord-021063-4y8m33ea 305 23 mediated mediate VBN cord-021063-4y8m33ea 305 24 by by IN cord-021063-4y8m33ea 305 25 specific specific JJ cord-021063-4y8m33ea 305 26 lipid lipid NN cord-021063-4y8m33ea 305 27 headgroups headgroups NNP cord-021063-4y8m33ea 305 28 and and CC cord-021063-4y8m33ea 305 29 surface surface NN cord-021063-4y8m33ea 305 30 charge charge NN cord-021063-4y8m33ea 305 31 density density NN cord-021063-4y8m33ea 305 32 Interactions interaction NNS cord-021063-4y8m33ea 305 33 of of IN cord-021063-4y8m33ea 305 34 mammalian mammalian JJ cord-021063-4y8m33ea 305 35 cells cell NNS cord-021063-4y8m33ea 305 36 with with IN cord-021063-4y8m33ea 305 37 lipid lipid NN cord-021063-4y8m33ea 305 38 dispersions dispersion NNS cord-021063-4y8m33ea 305 39 containing contain VBG cord-021063-4y8m33ea 305 40 novel novel NN cord-021063-4y8m33ea 305 41 metabolizable metabolizable JJ cord-021063-4y8m33ea 305 42 cationic cationic JJ cord-021063-4y8m33ea 305 43 amphiphiles amphiphile NNS cord-021063-4y8m33ea 305 44 . . . cord-021063-4y8m33ea 306 1 B B NNP cord-021063-4y8m33ea 306 2 iochim iochim NNP cord-021063-4y8m33ea 306 3 . . . cord-021063-4y8m33ea 307 1 B B NNP cord-021063-4y8m33ea 307 2 iophys iophys NNP cord-021063-4y8m33ea 307 3 pH ph NN cord-021063-4y8m33ea 307 4 - - HYPH cord-021063-4y8m33ea 307 5 sensitive sensitive JJ cord-021063-4y8m33ea 307 6 , , , cord-021063-4y8m33ea 307 7 plasma plasma NN cord-021063-4y8m33ea 307 8 - - HYPH cord-021063-4y8m33ea 307 9 stable stable JJ cord-021063-4y8m33ea 307 10 liposomes liposome NNS cord-021063-4y8m33ea 307 11 with with IN cord-021063-4y8m33ea 307 12 relatively relatively RB cord-021063-4y8m33ea 307 13 prolonged prolong VBN cord-021063-4y8m33ea 307 14 residence residence NN cord-021063-4y8m33ea 307 15 in in IN cord-021063-4y8m33ea 307 16 circulation circulation NN cord-021063-4y8m33ea 308 1 Optimized optimized JJ cord-021063-4y8m33ea 308 2 procedures procedure NNS cord-021063-4y8m33ea 308 3 for for IN cord-021063-4y8m33ea 308 4 the the DT cord-021063-4y8m33ea 308 5 coupling coupling NN cord-021063-4y8m33ea 308 6 of of IN cord-021063-4y8m33ea 308 7 proteins protein NNS cord-021063-4y8m33ea 308 8 to to IN cord-021063-4y8m33ea 308 9 liposomes liposome VBN cord-021063-4y8m33ea 308 10 Vesicles Vesicles NNP cord-021063-4y8m33ea 308 11 of of IN cord-021063-4y8m33ea 308 12 variable variable JJ cord-021063-4y8m33ea 308 13 sizes size NNS cord-021063-4y8m33ea 308 14 produced produce VBN cord-021063-4y8m33ea 308 15 by by IN cord-021063-4y8m33ea 308 16 a a DT cord-021063-4y8m33ea 308 17 rapid rapid JJ cord-021063-4y8m33ea 308 18 extrusion extrusion NN cord-021063-4y8m33ea 308 19 procedure procedure NN cord-021063-4y8m33ea 308 20 Karyophilic Karyophilic NNP cord-021063-4y8m33ea 308 21 properties property NNS cord-021063-4y8m33ea 308 22 of of IN cord-021063-4y8m33ea 308 23 Semliki Semliki NNP cord-021063-4y8m33ea 308 24 Forest Forest NNP cord-021063-4y8m33ea 308 25 virus virus NN cord-021063-4y8m33ea 308 26 nucleocapsid nucleocapsid NN cord-021063-4y8m33ea 308 27 protein protein NNP cord-021063-4y8m33ea 308 28 Human human JJ cord-021063-4y8m33ea 308 29 gene gene NN cord-021063-4y8m33ea 308 30 therapy therapy NN cord-021063-4y8m33ea 308 31 Direct direct JJ cord-021063-4y8m33ea 308 32 gene gene NN cord-021063-4y8m33ea 308 33 transfer transfer NN cord-021063-4y8m33ea 308 34 with with IN cord-021063-4y8m33ea 308 35 DNA dna NN cord-021063-4y8m33ea 308 36 - - HYPH cord-021063-4y8m33ea 308 37 liposome liposome NN cord-021063-4y8m33ea 308 38 complexes complex NNS cord-021063-4y8m33ea 308 39 in in IN cord-021063-4y8m33ea 308 40 melanoma melanoma NN cord-021063-4y8m33ea 308 41 : : : cord-021063-4y8m33ea 308 42 expression expression NN cord-021063-4y8m33ea 308 43 , , , cord-021063-4y8m33ea 308 44 biologic biologic JJ cord-021063-4y8m33ea 308 45 activity activity NN cord-021063-4y8m33ea 308 46 , , , cord-021063-4y8m33ea 308 47 and and CC cord-021063-4y8m33ea 308 48 lack lack NN cord-021063-4y8m33ea 308 49 of of IN cord-021063-4y8m33ea 308 50 toxicity toxicity NN cord-021063-4y8m33ea 308 51 in in IN cord-021063-4y8m33ea 308 52 humans human NNS cord-021063-4y8m33ea 309 1 The the DT cord-021063-4y8m33ea 309 2 improved improved JJ cord-021063-4y8m33ea 309 3 efficient efficient JJ cord-021063-4y8m33ea 309 4 method method NN cord-021063-4y8m33ea 309 5 for for IN cord-021063-4y8m33ea 309 6 introducing introduce VBG cord-021063-4y8m33ea 309 7 macromolecules macromolecule NNS cord-021063-4y8m33ea 309 8 into into IN cord-021063-4y8m33ea 309 9 cells cell NNS cord-021063-4y8m33ea 309 10 using use VBG cord-021063-4y8m33ea 309 11 HVJ HVJ NNP cord-021063-4y8m33ea 309 12 ( ( -LRB- cord-021063-4y8m33ea 309 13 Sendai Sendai NNP cord-021063-4y8m33ea 309 14 virus virus NN cord-021063-4y8m33ea 309 15 ) ) -RRB- cord-021063-4y8m33ea 309 16 liposomes liposome VBN cord-021063-4y8m33ea 309 17 with with IN cord-021063-4y8m33ea 309 18 gangliosides ganglioside NNS cord-021063-4y8m33ea 309 19 Fusion Fusion NNP cord-021063-4y8m33ea 309 20 of of IN cord-021063-4y8m33ea 309 21 influenza influenza NN cord-021063-4y8m33ea 309 22 virus virus NN cord-021063-4y8m33ea 309 23 particles particle NNS cord-021063-4y8m33ea 309 24 with with IN cord-021063-4y8m33ea 309 25 liposomes liposome NNS cord-021063-4y8m33ea 309 26 : : : cord-021063-4y8m33ea 310 1 Requirement requirement NN cord-021063-4y8m33ea 310 2 for for IN cord-021063-4y8m33ea 310 3 cholesterol cholesterol NN cord-021063-4y8m33ea 310 4 and and CC cord-021063-4y8m33ea 310 5 virus virus NN cord-021063-4y8m33ea 310 6 receptors receptor NNS cord-021063-4y8m33ea 310 7 to to TO cord-021063-4y8m33ea 310 8 allow allow VB cord-021063-4y8m33ea 310 9 fusion fusion NN cord-021063-4y8m33ea 310 10 with with IN cord-021063-4y8m33ea 310 11 and and CC cord-021063-4y8m33ea 310 12 lysis lysis NN cord-021063-4y8m33ea 310 13 of of IN cord-021063-4y8m33ea 310 14 neutral neutral JJ cord-021063-4y8m33ea 310 15 but but CC cord-021063-4y8m33ea 310 16 not not RB cord-021063-4y8m33ea 310 17 negatively negatively RB cord-021063-4y8m33ea 310 18 charged charge VBN cord-021063-4y8m33ea 310 19 liposomes liposome NNS cord-021063-4y8m33ea 310 20 Gene Gene NNP cord-021063-4y8m33ea 310 21 therapy therapy NN cord-021063-4y8m33ea 310 22 for for IN cord-021063-4y8m33ea 310 23 the the DT cord-021063-4y8m33ea 310 24 treatment treatment NN cord-021063-4y8m33ea 310 25 of of IN cord-021063-4y8m33ea 310 26 brain brain NN cord-021063-4y8m33ea 310 27 tumors tumor NNS cord-021063-4y8m33ea 310 28 using use VBG cord-021063-4y8m33ea 310 29 intra intra JJ cord-021063-4y8m33ea 310 30 - - JJ cord-021063-4y8m33ea 310 31 tumoral tumoral JJ cord-021063-4y8m33ea 310 32 transduction transduction NN cord-021063-4y8m33ea 310 33 with with IN cord-021063-4y8m33ea 310 34 the the DT cord-021063-4y8m33ea 310 35 thymidine thymidine NN cord-021063-4y8m33ea 310 36 kinase kinase NN cord-021063-4y8m33ea 310 37 gene gene NN cord-021063-4y8m33ea 310 38 and and CC cord-021063-4y8m33ea 310 39 intravenous intravenous JJ cord-021063-4y8m33ea 310 40 ganciclovir ganciclovir NN cord-021063-4y8m33ea 310 41 Heterologous Heterologous NNP cord-021063-4y8m33ea 310 42 introns intron NNS cord-021063-4y8m33ea 310 43 can can MD cord-021063-4y8m33ea 310 44 enhance enhance VB cord-021063-4y8m33ea 310 45 expression expression NN cord-021063-4y8m33ea 310 46 oftransgenes oftransgene NNS cord-021063-4y8m33ea 310 47 in in IN cord-021063-4y8m33ea 310 48 mice mouse NNS cord-021063-4y8m33ea 310 49 Cochleate Cochleate NNP cord-021063-4y8m33ea 310 50 lipid lipid NN cord-021063-4y8m33ea 310 51 cylinders cylinder NNS cord-021063-4y8m33ea 310 52 : : : cord-021063-4y8m33ea 310 53 formation formation NN cord-021063-4y8m33ea 310 54 by by IN cord-021063-4y8m33ea 310 55 fusion fusion NN cord-021063-4y8m33ea 310 56 of of IN cord-021063-4y8m33ea 310 57 unilamellar unilamellar JJ cord-021063-4y8m33ea 310 58 lipid lipid NN cord-021063-4y8m33ea 310 59 vesicles vesicle NNS cord-021063-4y8m33ea 311 1 Targeted target VBN cord-021063-4y8m33ea 311 2 integration integration NN cord-021063-4y8m33ea 311 3 of of IN cord-021063-4y8m33ea 311 4 adeno adeno NN cord-021063-4y8m33ea 311 5 - - HYPH cord-021063-4y8m33ea 311 6 associated associate VBN cord-021063-4y8m33ea 311 7 virus virus NN cord-021063-4y8m33ea 311 8 ( ( -LRB- cord-021063-4y8m33ea 311 9 AAV AAV NNP cord-021063-4y8m33ea 311 10 ) ) -RRB- cord-021063-4y8m33ea 311 11 into into IN cord-021063-4y8m33ea 311 12 human human JJ cord-021063-4y8m33ea 311 13 chromosome chromosome NN cord-021063-4y8m33ea 311 14 19 19 CD cord-021063-4y8m33ea 311 15 Endocytosis Endocytosis NNP cord-021063-4y8m33ea 311 16 and and CC cord-021063-4y8m33ea 311 17 intracellular intracellular JJ cord-021063-4y8m33ea 311 18 fate fate NN cord-021063-4y8m33ea 311 19 of of IN cord-021063-4y8m33ea 311 20 liposomes liposome NNS cord-021063-4y8m33ea 311 21 using use VBG cord-021063-4y8m33ea 311 22 pyranine pyranine NNP cord-021063-4y8m33ea 311 23 as as IN cord-021063-4y8m33ea 311 24 probe probe NN cord-021063-4y8m33ea 311 25 Aerosol Aerosol NNP cord-021063-4y8m33ea 311 26 gene gene NN cord-021063-4y8m33ea 311 27 delivery delivery NN cord-021063-4y8m33ea 311 28 in in IN cord-021063-4y8m33ea 311 29 vivo vivo NN cord-021063-4y8m33ea 311 30 Entrapment entrapment NN cord-021063-4y8m33ea 311 31 of of IN cord-021063-4y8m33ea 311 32 high high JJ cord-021063-4y8m33ea 311 33 - - HYPH cord-021063-4y8m33ea 311 34 molecular molecular JJ cord-021063-4y8m33ea 311 35 - - HYPH cord-021063-4y8m33ea 311 36 mass mass NN cord-021063-4y8m33ea 311 37 DNA dna NN cord-021063-4y8m33ea 311 38 molecules molecule NNS cord-021063-4y8m33ea 311 39 in in IN cord-021063-4y8m33ea 311 40 liposomes liposome NNS cord-021063-4y8m33ea 311 41 for for IN cord-021063-4y8m33ea 311 42 the the DT cord-021063-4y8m33ea 311 43 genetic genetic JJ cord-021063-4y8m33ea 311 44 transformation transformation NN cord-021063-4y8m33ea 311 45 of of IN cord-021063-4y8m33ea 311 46 animal animal NN cord-021063-4y8m33ea 311 47 cells cell NNS cord-021063-4y8m33ea 311 48 Transfer transfer NN cord-021063-4y8m33ea 311 49 of of IN cord-021063-4y8m33ea 311 50 condensed condense VBN cord-021063-4y8m33ea 311 51 viral viral JJ cord-021063-4y8m33ea 311 52 DNA dna NN cord-021063-4y8m33ea 311 53 into into IN cord-021063-4y8m33ea 311 54 eukaryotic eukaryotic JJ cord-021063-4y8m33ea 311 55 cells cell NNS cord-021063-4y8m33ea 311 56 using use VBG cord-021063-4y8m33ea 311 57 proteoliposomes proteoliposome NNS cord-021063-4y8m33ea 311 58 Direct direct JJ cord-021063-4y8m33ea 311 59 in in IN cord-021063-4y8m33ea 311 60 vivo vivo NN cord-021063-4y8m33ea 311 61 gene gene NN cord-021063-4y8m33ea 311 62 introduction introduction NN cord-021063-4y8m33ea 311 63 into into IN cord-021063-4y8m33ea 311 64 rat rat NN cord-021063-4y8m33ea 311 65 kidney kidney NN cord-021063-4y8m33ea 311 66 Membrane membrane NN cord-021063-4y8m33ea 311 67 fusion fusion NN cord-021063-4y8m33ea 311 68 proteins protein NNS cord-021063-4y8m33ea 311 69 of of IN cord-021063-4y8m33ea 311 70 enveloped envelop VBN cord-021063-4y8m33ea 311 71 animal animal NN cord-021063-4y8m33ea 311 72 viruses virus NNS