ArticlePLoS pathogens2010
Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
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- Adeno-Associated Virus Type 2 and Human Adenovirus Species F Type 41 Co-infection Associated with Acute Severe Hepatitis in Children, California, USA.Emerging infectious diseases · 2026Article
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Transient overexpression of hPKM2 in porcine cardiomyocytes prevents heart failure after myocardial infarction.Nature communications · 2025Article
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Review
- Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting.Nucleic acids research · 2025Article
- UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Recent advances in various adeno-associated viruses (AAVs) as gene therapy agents in hepatocellular carcinoma.Virology journal · 2024Review
- Article
- AAV genome modification for efficient AAV production.Heliyon · 2023Review
- AAV- based vector improvements unrelated to capsid protein modification.Frontiers in medicine · 2023Review
- Current Advances in Adeno-Associated Virus-Mediated Gene Therapy to Prevent Acquired Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2022Review
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Durability of transgene expression after rAAV gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- The adeno-associated virus 2 genome and Rep 68/78 proteins interact with cellular sites of DNA damage.Human molecular genetics · 2022Article
- Development of an Adeno-Associated Virus-Vectored SARS-CoV-2 Vaccine and Its Immunogenicity in Mice.Frontiers in cellular and infection microbiology · 2022Article
- Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics.Virology journal · 2021Review
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease.Human gene therapy · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.