Site-specific integration by adeno-associated virus

R. Michael Linden, Peter Ward, Catherine Giraud, Ernest Winocour, Kenneth I. Berns

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)11288-11294
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - 15 Oct 1996
Externally publishedYes

Keywords

  • DNA replication
  • gene therapy
  • parvovirus
  • recombination
  • targeted integration

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