Site-specific integration by adeno-associated virus

被引:217
|
作者
Linden, RM
Ward, P
Giraud, C
Winocour, E
Berns, KI
机构
[1] CORNELL UNIV MED COLL,HEARST MICROBIOL RES CTR,DEPT MICROBIOL,NEW YORK,NY 10021
[2] WEIZMANN INST SCI,DEPT MOL GENET,IL-76100 REHOVOT,ISRAEL
关键词
parvovirus; gene therapy; targeted integration; DNA replication; recombination;
D O I
10.1073/pnas.93.21.11288
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene delivery. Wild-type virus is notable for the lack of association with any human disease and the ability to stably integrate its genome in a site-specific manner in a locus on human chromosome 19 (AAVS1). Use of a functional model system for AAV DNA integration into AAVS1 has allowed us to conclude that the recombination event is directed by cellular DNA sequences. Recombinant junctions isolated from our integration assay were analyzed and showed characteristics similar to those found in latently infected cell lines. The minimal DNA signals within AAVS1 required for targeted integration were identified and shown to contain functional motifs of the viral origin of replication. A replication mediated model of AAV DNA integration is proposed.
引用
收藏
页码:11288 / 11294
页数:7
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