ArticleProceedings of the National Academy of Sciences of the United States of America2009
Site-specific integration of adeno-associated virus involves partial duplication of the target locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- 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
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Gene editing enables non-invasiveMolecular therapy. Methods & clinical development · 2025Article
- Structure and repair of replication-coupled DNA breaks.Science (New York, N.Y.) · 2024Article
- Cryo-EM Structure of AAV2 Rep68 bound to integration site AAVS1: Insights into the mechanism of DNA melting.bioRxiv : the preprint server for biology · 2024Article
- Clinical applications of gene therapy for rare diseases: A review.International journal of experimental pathology · 2023Review
- Reversed Phase-Liquid Chromatography for Recombinant AAV Genome Integrity Assessment.Analytical chemistry · 2023Article
- Potential Application of Optogenetic Stimulation in the Treatment of Pain and Migraine Headache: A Perspective from Animal Studies.Brain sciences · 2019Review
- Exchange of functional domains between a bacterial conjugative relaxase and the integrase of the human adeno-associated virus.PloS one · 2018Article
- The Different Faces of Rolling-Circle Replication and Its Multifunctional Initiator Proteins.Frontiers in microbiology · 2017Review
- Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Review
- Role of Neuromodulation and Optogenetic Manipulation in Pain Treatment.Current neuropharmacology · 2016Review
- Structural Insights into the Assembly of the Adeno-associated Virus Type 2 Rep68 Protein on the Integration Site AAVS1.The Journal of biological chemistry · 2015Article
- Presence of a trs-Like Motif Promotes Rep-Mediated Wild-Type Adeno-Associated Virus Type 2 Integration.Journal of virology · 2015Article
- Article
- An AAVS1-targeted minigene platform for correction of iPSCs from all five types of chronic granulomatous disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease.Neurobiology of aging · 2014Article
- Genomic editing tools to model human diseases with isogenic pluripotent stem cells.Stem cells and development · 2014Review
- Adeno-associated virus Rep represses the human integration site promoter by two pathways that are similar to those required for the regulation of the viral p5 promoter.Journal of virology · 2014Article
- Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis.Haematologica · 2014Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
A variety of viruses establish latency by integrating their genome into the host genome. The integration event generally occurs in a nonspecific manner, precluding the prediction of functional consequences from resulting disruptions of affected host genes. The nonpathogenic adeno-associated virus (AAV) is unique in its ability to stably integrate in a site-specific manner into the human MBS85 gene. To gain a better understanding of the integration mechanism and the consequences of MBS85 disruption, we analyzed the molecular structure of AAV integrants in various latently infected human cell lines. Our study led to the observation that AAV integration causes an extensive but partial duplication of the target gene. Intriguingly, the molecular organization of the integrant leaves the possibility that a functional copy of the disrupted target gene could potentially be preserved despite the resulting rearrangements. A latently infected, Mbs85-targeted mouse ES cell line was generated to study the functional consequences of the observed duplication-based integration mechanism. AAV-modified ES cell lines continued to self-renew, maintained their multilineage differentiation potential and contributed successfully to mouse development when injected into blastocysts. Thus, our study reveals a viral strategy for targeted genome addition with the apparent absence of functional consequences.
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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.