Site-specific integration by adeno-associated virus.

作者：R. Michael Linden, Peter B. Ward, Catherine Giraud, Ernest Winocour, Kenneth I. Berns · 发表于：Proceedings of the National Academy of Sciences · 年份：1996 · DOI：10.1073/pnas.93.21.11288 · 被引用次数：808 · 研究领域：Virus-based gene therapy research、CRISPR and Genetic Engineering、Viral gastroenteritis research and epidemiology

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.