Integration of Adeno-Associated Virus (AAV) and Recombinant AAV Vectors
Abstract
The driving interest in adeno-associated virus (AAV) has been its potential as a gene delivery vector. The early observation that AAV can establish a latent infection by integrating into the host chromosome has been central to this interest. However, chromosomal integration is a two-edged sword, imparting on one hand the ability to maintain the therapeutic gene in progeny cells, and on the other hand, the risk of mutations that are deleterious to the host. A clearer understanding of the mechanism and efficiency of AAV integration, in terms of contributing viral and host-cell factors and circumstances, will provide a context in which to evaluate these potential benefits and risks. Research to date suggests that AAV integration in any context is inefficient, and that the persistence of AAV gene delivery vectors in tissues is largely attributable to episomal genomes.
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Subsequent to infection, recombinant AAV can express a therapeutic gene and persist without integration into the host genome by existing episomally in circular head-to-tail concatemers.
“Subsequent to infection, rAAV can express the therapeutic gene and persist without integration into the host genome by existing episomally in circular head-to-tail concatemers (29).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [29]
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- Authors
- McCarty, D. M., Young, S. M., & Samulski, R. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Salk Institute for Biological Studies (US)
- Venue
- Annual Review of Genetics
- Publisher
- Annual Reviews
- Published
- 2004-12-01
- Volume
- 38
- Issue
- 1
- Pages
- 819-845
- ISSN
- 0066-4197 (ISSN-L)
- 1545-2948
- OpenAlex
- W2151316131
- Cited by
- 450
- References
- 8
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 26 · 2023: 19 · 2022: 14 · 2021: 15 · 2020: 25 · 2019: 13 · 2018: 13 · 2017: 14 · 2016: 17 · 2015: 27 · 2014: 16 · 2013: 14 · 2012: 12
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Keywords
- adeno-associated virus, AAV integration, chromosomal integration, recombinant AAV vectors, gene delivery vectors, latent infection, host cell factors, integration efficiency
- MeSH terms
- Dependovirus, Cell Line, Chromosomes, Human, Pair 19, DNA, Genetic Vectors, HeLa Cells, Humans, Recombination, Genetic, Genetic Therapy, Virus Integration, Genome, Viral
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