ArticleNucleic acids research2006
Homologous recombination is required for AAV-mediated gene targeting.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- AAV-mediated genome editing is influenced by the formation of R-loops.bioRxiv : the preprint server for biology · 2024Article
- Targeted long-read sequencing captures CRISPR editing and AAV integration outcomes in brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- In search of an ideal template for therapeutic genome editing: A review of current developments for structure optimization.Frontiers in genome editing · 2023Review
- Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice.Nature biotechnology · 2022Article
- Generation of scalable cancer models by combining AAV-intron-trap, CRISPR/Cas9, and inducible Cre-recombinase.Communications biology · 2021Article
- Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Improved Genome Editing through Inhibition of FANCM and Members of the BTR Dissolvase Complex.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- The Role of Recombinant AAV in Precise Genome Editing.Frontiers in genome editing · 2021Review
- Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.Human gene therapy · 2020Review
- Molecular characterization of precise in vivo targeted gene integration in human cells using AAVHSC15.PloS one · 2020Article
- DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Robust Generation of Knock-in Cell Lines Using CRISPR-Cas9 and rAAV-assisted Repair Template Delivery.Bio-protocol · 2017Article
- Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing.Advances in experimental medicine and biology · 2017Review
- CRISPR/Cas9-AAV Mediated Knock-in at NRL Locus in Human Embryonic Stem Cells.Molecular therapy. Nucleic acids · 2016Article
- Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template.Science translational medicine · 2015Article
- Adeno-associated Virus as a Mammalian DNA Vector.Microbiology spectrum · 2015Review
- A genome-wide map of adeno-associated virus-mediated human gene targeting.Nature structural & molecular biology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High frequencies of gene targeting can be achieved by infection of mammalian cells with recombinant adeno-associated virus (rAAV) vectors [D. W. Russell and R. K. Hirata (1998) Nature Genet., 18, 325-330; D. W. Russell and R. K. Hirata (2000) J. Virol., 74, 4612-4620; R. Hirata et al. (2002) Nat. Biotechnol., 20, 735-738], but the mechanism of targeting is unclear and random integration often occurs in parallel. We assessed the role of specific DNA repair and recombination pathways in rAAV gene targeting by measuring correction of a mutated enhanced green fluorescent protein (EGFP) gene in cells where homologous recombination (HR) or non-homologous end-joining (NHEJ) had been suppressed by RNAi. EGFP-negative cells were transduced with rAAV vectors carrying a different inactivating deletion in the EGFP, and in parallel with rAAV vectors carrying red fluorescent protein (RFP). Expression of RFP accounted for viral transduction efficiency and long-term random integration. Approximately 0.02% of the infected GFP-negative cells were stably converted to GFP positive cells. Silencing of the essential NHEJ component DNA-PK had no significant effect on the frequency of targeting at any time point examined. Silencing of the SNF2/SWI2 family members RAD54L or RAD54B, which are important for HR, reduced the rate of stable rAAV gene targeting approximately 5-fold. Further, partial silencing of the Rad51 paralogue XRCC3 completely abolished stable long-term EGFP expression. These results show that rAAV gene targeting requires the Rad51/Rad54 pathway of HR.
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