ArticleMolecular and cellular biology2003
Human gene targeting by adeno-associated virus vectors is enhanced by 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 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
62 citing papers in PubMed, 125 citations in OpenAlex.
- AviTag-seq unifies nucleotide-resolution maps of CRISPR off-targets and AAV vector integrations.Communications biology · 2026Article
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- Efficient Gene-Editing in Human Pluripotent Stem Cells Through Simplified Assembly of Adeno-Associated Viral (AAV) Donor Templates.Bio-protocol · 2024Article
- Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice.Blood · 2023Article
- 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
- Genetic therapies for neurological disorders.Human genetics · 2022Review
- New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- AAV-mediated gene editing lights up the lung.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
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- The TRACE-Seq method tracks recombination alleles and identifies clonal reconstitution dynamics of gene targeted human hematopoietic stem cells.Nature communications · 2021Article
- The Role of Recombinant AAV in Precise Genome Editing.Frontiers in genome editing · 2021Review
- Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction.Human gene therapy · 2020Review
- High levels of AAV vector integration into CRISPR-induced DNA breaks.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
- CRISPR/Cas9 genome editing in human hematopoietic stem cells.Nature protocols · 2018Article
- Delivery technologies for genome editing.Nature reviews. Drug discovery · 2017Review
- Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Recombinant AAV Integration Is Not Associated With Hepatic Genotoxicity in Nonhuman Primates and Patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes.Molecular therapy. Nucleic acids · 2016Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The use of adeno-associated virus (AAV) to package gene-targeting vectors as single-stranded linear molecules has led to significant improvements in mammalian gene-targeting frequencies. However, the molecular basis for the high targeting frequencies obtained is poorly understood, and there could be important mechanistic differences between AAV-mediated gene targeting and conventional gene targeting with transfected double-stranded DNA constructs. Conventional gene targeting is thought to occur by the double-strand break (DSB) model of homologous recombination, as this can explain the higher targeting frequencies observed when DSBs are present in the targeting construct or target locus. Here we compare AAV-mediated gene-targeting frequencies in the presence and absence of induced target site DSBs. Retroviral vectors were used to introduce a mutant lacZ gene containing an I-SceI cleavage site and to efficiently deliver the I-SceI endonuclease, allowing us to carry out these studies with normal and transformed human cells. Creation of DSBs by I-SceI increased AAV-mediated gene-targeting frequencies 60- to 100-fold and resulted in a precise correction of the mutant lacZ reporter gene. These experiments demonstrate that AAV-mediated gene targeting can result in repair of a DNA DSB and that this form of gene targeting exhibits fundamental similarities to conventional gene targeting. In addition, our findings suggest that the selective creation of DSBs by using viral delivery systems can increase gene-targeting frequencies in scientific and therapeutic applications.
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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.