ArticleNature biotechnology2025
Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Precise, predictable genome integrations by deep-learning-assisted design of microhomology-based templates.Nature biotechnology · 2026Article
- Multilevel characterization of genome editor nuclease activity with BreakTag.Nature protocols · 2026Review
- Deep learning-driven prediction of on-target activity, off-target risk, and repair outcomes in CRISPR/Cas9: current landscape and multi-scale perspectives.Journal of translational medicine · 2026Review
- Indel pattern-guided repair mapping reveals genome-wide DNA repair networks in CRISPR/Cas9 editing.Nucleic acids research · 2026Article
- ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks.Nature communications · 2026Article
- Nanocarrier-mediated CRISPR-Cas delivery: a novel approach against antibiotic-resistant superbugs.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Assessing off-target effects in CRISPR/Cas9: challenges and strategies for precision DNA editing.Archives of microbiology · 2026Review
- Circular single stranded DNA potentiates non-viral gene insertion in hematopoietic stem and progenitor cells.Nature communications · 2025Article
- Characterizing and controlling CRISPR repair outcomes in nondividing human cells.Nature communications · 2025Article
- Increasing Cas12a- and Cas9-mediated deletion sizes with exonucleases.Plant physiology · 2025Article
- A single donor cassette enables site-specific knock-in at either the αAmy3 or αAmy8 locus in rice cells via CRISPR/Cas9.Applied microbiology and biotechnology · 2025Article
- [Advances in the application strategies of CRISPR/Cas9 technology in chimeric antigen receptor T cell therapy for hematological malignancies].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag.Nature biotechnology · 2025Article
- Catalase-Knockout Complements the Radio-Sensitization Effect of Titanium Peroxide Nanoparticles on Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2025Article
- A long journey towards genome editing technologies in plants: a technical and critical review of genome editing technologies.Frontiers in genome editing · 2025Review
- The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations.Nature communications · 2024Article
- DeepIndel: An Interpretable Deep Learning Approach for Predicting CRISPR/Cas9-Mediated Editing Outcomes.International journal of molecular sciences · 2024Article
- Context effects on repair of 5'-overhang DNA double-strand breaks induced by Cas12a in Arabidopsis.Plant direct · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Cas9 can cleave DNA in both blunt and staggered configurations, resulting in distinct editing outcomes, but what dictates the type of Cas9 incisions is largely unknown. In this study, we developed BreakTag, a versatile method for profiling Cas9-induced DNA double-strand breaks (DSBs) and identifying the determinants of Cas9 incisions. Overall, we assessed cleavage by SpCas9 at more than 150,000 endogenous on-target and off-target sites targeted by approximately 3,500 single guide RNAs. We found that approximately 35% of SpCas9 DSBs are staggered, and the type of incision is influenced by DNA:gRNA complementarity and the use of engineered Cas9 variants. A machine learning model shows that Cas9 incision is dependent on the protospacer sequence and that human genetic variation impacts the configuration of Cas9 cuts and the DSB repair outcome. Matched datasets of Cas9 and engineered variant incisions with repair outcomes show that Cas9-mediated staggered breaks are linked with precise, templated and predictable single-nucleotide insertions, demonstrating that a scission-based gRNA design can be used to correct clinically relevant pathogenic single-nucleotide deletions.
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