Sites of recombinant adeno-associated virus integration.

Published

Journal Article

Adeno-associated virus (AAV), a defective parvovirus, is considered a promising vector for the delivery of therapeutic genes to cells. Both wild-type and recombinant AAV display a wide tropism and integrate into the host genome, in the absence of helper virus, establishing a latent infection. A unique characteristic of wild-type AAV and a potential advantage for use as a delivery system for gene therapy is the site-specific integration of wild-type virus within a small region of chromosome 19, 19q13.3-qter (AAVS1), in up to 85% of cell lines infected with the virus. Although recombinant AAVs, containing only the inverted terminal repeats of wild-type virus, can integrate efficiently into the host genome, specificity for the AAVS1 site appears to be lost. To address this question, the integration characteristics of two recombinant AAVs lacking the rep and cap genes in HeLa cells were examined. Analysis of Southern blots indicated that none of twenty-six cell clones generated after infection with either one of the recombinant AAVs demonstrated integration within the AAVS1 locus on chromo-some 19. Analysis of five of the cell lines by fluorescent chromosome in situ hybridization confirmed the loss of chromosome 19 specificity. Each integration site mapped near a known fragile site and/or location of a proto-oncogene or growth regulatory gene. Retention of site-specific integration of wild-type AAV will require the inclusion of additional AAV-specific sequences within the recombinant vectors.

Full Text

Duke Authors

Cited Authors

  • Rivadeneira, ED; Popescu, NC; Zimonjic, DB; Cheng, GS; Nelson, PJ; Ross, MD; DiPaolo, JA; Klotman, ME

Published Date

  • April 1998

Published In

Volume / Issue

  • 12 / 4

Start / End Page

  • 805 - 810

PubMed ID

  • 9499439

Pubmed Central ID

  • 9499439

International Standard Serial Number (ISSN)

  • 1019-6439

Digital Object Identifier (DOI)

  • 10.3892/ijo.12.4.805

Language

  • eng

Conference Location

  • Greece