ArticleBMC genomics2020
ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing.
Article in BMC genomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- intmap: fast and flexible mapping of mobile DNA integration for basic and translational research.Bioinformatics (Oxford, England) · 2026Article
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome.Gene therapy · 2026Article
- Engineering a streamlined virus-like particle for programmable tissue-specific gene delivery.Nature communications · 2025Article
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- The hidden risks of CRISPR/Cas: structural variations and genome integrity.Nature communications · 2025Review
- Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- CRISPR/Cas9 gene therapy increases the risk of tumorigenesis in the mouse model of hereditary tyrosinemia type I.JHEP reports : innovation in hepatology · 2025Article
- 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
- Rescue of the endogenous FVIII expression in hemophilia A mice using CRISPR-Cas9 mRNA LNPs.Molecular therapy. Nucleic acids · 2024Article
- Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.Nature biotechnology · 2024Article
- Recent Advances in Gene Therapy for Hemophilia: Projecting the Perspectives.Biomolecules · 2024Review
- Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.Hepatology communications · 2024Article
- Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.EMBO molecular medicine · 2024Article
- CRISPR-Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications.Nature communications · 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
- Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing.Nature communications · 2023Review
- Extru-seq: a method for predicting genome-wide Cas9 off-target sites with advantages of both cell-based and in vitro approaches.Genome biology · 2023Article
- TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor.Nature communications · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIdentifying nuclease-induced double-stranded breaks in DNA on a genome-wide scale is critical for assessing the safety and efficacy of genome editing therapies. We previously demonstrated that after administering adeno-associated viral (AAV) vector-mediated genome-editing strategies in vivo, vector sequences integrated into the host organism's genomic DNA at double-stranded breaks. Thus, identifying the genomic location of inserted AAV sequences would enable us to identify DSB events, mainly derived from the nuclease on- and off-target activity.
resultsHere, we developed a next-generation sequencing assay that detects insertions of specific AAV vector sequences called inverted terminal repeats (ITRs). This assay, ITR-Seq, enables us to identify off-target nuclease activity in vivo. Using ITR-Seq, we analyzed liver DNA samples of rhesus macaques treated with AAV vectors expressing a meganuclease. We found dose-dependent off-target activity and reductions in off-target events induced by further meganuclease development. In mice, we identified the genomic locations of ITR integration after treatment with Cas9 nucleases and their corresponding single-guide RNAs.
conclusionsIn sum, ITR-Seq is a powerful method for identifying off-target sequences induced by AAV vector-delivered genome-editing nucleases. ITR-Seq will help us understand the specificity and efficacy of different genome-editing nucleases in animal models and clinical studies. This information can help enhance the safety profile of gene-editing therapies.
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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.