ArticleMolecular and cellular biology2003
Efficient gene targeting mediated by adeno-associated virus and DNA double-strand breaks.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
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- Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation.Nucleic acids research · 2025Article
- A differentiated β-globin gene replacement strategy uses heterologous introns to restore physiological expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Efficient Gene-Editing in Human Pluripotent Stem Cells Through Simplified Assembly of Adeno-Associated Viral (AAV) Donor Templates.Bio-protocol · 2024Article
- Targeted Delivery of Chimeric Antigen Receptor into T Cells via CRISPR-Mediated Homology-Directed Repair with a Dual-AAV6 Transduction System.Current issues in molecular biology · 2023Article
- Rare immune diseases paving the road for genome editing-based precision medicine.Frontiers in genome editing · 2023Review
- Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice.Nature biotechnology · 2022Article
- Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.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
- A primer to gene therapy: Progress, prospects, and problems.Journal of inherited metabolic disease · 2021Review
- Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction.Human gene therapy · 2020Review
- Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.Human gene therapy · 2020Review
- Article
- Molecular characterization of precise in vivo targeted gene integration in human cells using AAVHSC15.PloS one · 2020Article
- Article
- AAV6 Is Superior to Clade F AAVs in Stimulating Homologous Recombination-Based Genome Editing in Human HSPCs.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Gene correction for SCID-X1 in long-term hematopoietic stem cells.Nature communications · 2019Article
- Global Transcriptional Response to CRISPR/Cas9-AAV6-Based Genome Editing in CD34Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- In Vivo Genome Editing as a Therapeutic Approach.International journal of molecular sciences · 2018Review
- Refinement of the endogenous epitope tagging technology allows the identification of a novel NRAS binding partner in melanoma.Pigment cell & melanoma research · 2018Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Gene targeting is the in situ manipulation of the sequence of an endogenous gene by the introduction of homologous exogenous DNA. Presently, the rate of gene targeting is too low for it to be broadly used in mammalian somatic cell genetics or to cure genetic diseases. Recently, it has been demonstrated that infection with recombinant adeno-associated virus (rAAV) vectors can mediate gene targeting in somatic cells, but the mechanism is unclear. This paper explores the balance between random integration and gene targeting with rAAV. Both random integration and spontaneous gene targeting are dependent on the multiplicity of infection (MOI) of rAAV. It has previously been shown that the introduction of a DNA double-stranded break (DSB) in a target gene can stimulate gene targeting by several-thousand-fold in somatic cells. Creation of a DSB stimulates the frequency of rAAV-mediated gene targeting by over 100-fold, suggesting that the mechanism of rAAV-mediated gene targeting involves, at least in part, the repair of DSBs by homologous recombination. Absolute gene targeting frequencies reach 0.8% with a dual vector system in which one rAAV vector provides a gene targeting substrate and a second vector expresses the nuclease that creates a DSB in the target gene. The frequencies of gene targeting that we achieved with relatively low MOIs suggest that combining rAAV vectors with DSBs is a promising strategy to broaden the application of gene targeting.
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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.