Packaging of Human Chromosome 19-Specific Adeno-Associated Virus (AAV) Integration Sites in AAV Virions during AAV Wild-Type and Recombinant AAV Vector Production
Open accessAbstract
Adeno-associated virus type 2 (AAV-2) establishes latency by site-specific integration into a unique locus on human chromosome 19, called AAVS1. During the development of a sensitive real-time PCR assay for site-specific integration, AAV-AAVS1 junctions were reproducibly detected in highly purified AAV wild-type and recombinant AAV vector stocks. A series of controls documented that the junctions were packaged in AAV capsids and were newly generated during a single round of AAV production. Cloned junctions displayed variable AAV sequences fused to AAVS1. These data suggest that packaged junctions represent footprints of AAV integration during productive infection. Apparently, AAV latency established by site-specific integration and the helper virus-dependent, productive AAV cycle are more closely related than previously thought.
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Genome sequences closely homologous to RBE, such as the AAVS1 site, have been detected in purified AAV vector preparations.
“It has been reported that genome sequences which are close homologs to RBE, such as, the AAVS1 site, were detected in purified AAV vector preparations [82].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [82]
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“Several investigators have shown that AAV DNA and heterologous, chromosomal DNA that contains a Rep binding element and a terminal resolution site, but no TRs, can also be packaged into AAV virions ( Huser et al., 2003; Nony et al., 2003).”
BackgroundUnderstanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses
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- Authors
- Hüser, D., Weger, S., & Heilbronn, R.
- Affiliations
- Department of Virology, Institute of Infectious Diseases, Free University of Berlin, 12203 Berlin, Germany
- Freie Universität Berlin (DE)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2003-04-15
- Volume
- 77
- Issue
- 8
- Pages
- 4881-4887
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC152110
- OpenAlex
- W2129504792
- Cited by
- 29
- References
- 0
- Citations by year
- 2023: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 506)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Keywords
- adeno-associated virus type 2, AAVS1, site-specific integration, viral latency, capsid, recombinant AAV vectors, productive infection, helper virus, real-time PCR
- MeSH terms
- Dependovirus, Chromosomes, Human, Pair 19, Genetic Vectors, HeLa Cells, Humans, Recombination, Genetic, Polymerase Chain Reaction, Virus Integration, Sequence Analysis, DNA, Virus Assembly
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