ArticleProceedings of the National Academy of Sciences of the United States of America2001
Adeno-associated virus (AAV) site-specific recombination does not require a Rep-dependent origin of replication within the AAV terminal repeat.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- A Comprehensive Study of the Effects by Sequence Truncation within Inverted Terminal Repeats (ITRs) on the Productivity, Genome Packaging, and Potency of AAV Vectors.Microorganisms · 2024Article
- AAV-based vectors for human diseases modeling in laboratory animals.Frontiers in medicine · 2024Review
- Endogenous viral elements: insights into data availability and accessibility.Virus evolution · 2024Article
- Article
- AAV- based vector improvements unrelated to capsid protein modification.Frontiers in medicine · 2023Review
- Cruciform DNA Structures Act as Legible Templates for Accelerating Homologous Recombination in Transgenic Animals.International journal of molecular sciences · 2022Article
- Virus-Host Coevolution with a Focus on Animal and Human DNA Viruses.Journal of molecular evolution · 2020Review
- Somatic Gene Editing ofHuman gene therapy · 2019Article
- Endogenous non-retroviral elements in genomes of Aedes mosquitoes and vector competence.Emerging microbes & infections · 2019Review
- Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease.Scientific reports · 2017Article
- The Different Faces of Rolling-Circle Replication and Its Multifunctional Initiator Proteins.Frontiers in microbiology · 2017Review
- 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
- Structural Studies of AAV2 Rep68 Reveal a Partially Structured Linker and Compact Domain Conformation.Biochemistry · 2015Article
- Adeno-associated virus type 2 preferentially integrates single genome copies with defined breakpoints.Virology journal · 2014Article
- High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration.Journal of virology · 2013Article
- Concerted nicking of donor and chromosomal acceptor DNA promotes homology-directed gene targeting in human cells.Nucleic acids research · 2012Article
- p53 inhibits adeno-associated viral vector integration.Human gene therapy · 2011Article
- Cardiac gene therapy with SERCA2a: from bench to bedside.Journal of molecular and cellular cardiology · 2011Review
- Virion-associated cofactor high-mobility group DNA-binding protein-1 facilitates transposition from the herpes simplex virus/Sleeping Beauty amplicon vector platform.Human gene therapy · 2010Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) is the only known eukaryotic virus capable of targeted integration in human cells. An AAV Rep binding element (RBE) and terminal resolution site (trs) identical to the viral terminal repeats required for AAV DNA replication are located on chromosome (ch) 19. Both ch-19 RBE and trs elements have been shown to be essential for viral targeting to this locus. To characterize the role of the AAV inverted terminal repeat (ITR) cis-acting sequences in targeted integration an AAV trs mutant incapable of supporting viral replication was tested. Wild-type and mutant substrates were assayed for targeted integration after cotransfection in the presence or absence of Rep. Our results demonstrated that, in the presence of Rep78, both ITR substrates targeted to ch-19 with similar frequency. Molecular characterization of the mutant ITR integrants confirmed the presence of the trs mutation in the majority of samples tested. Complementation analysis confirmed that the mutant targeted viral genomes were unable to rescue and replicate. In addition, Rep78 induced extensive rearrangement and amplification of ch-19 sequences independent of wild-type or mutant targeting substrate. These studies demonstrate that Rep-dependent nicking of the viral cis-acting trs sequence is not a prerequisite for site-specific recombination and suggests AAV targeting is mediated by Rep78/68-dependent replication from the ch-19 origin of replication (ori). These studies have significant impact toward the understanding of AAV site-specific recombination and the development of targeting vectors.
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Registered trials
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.