ArticleNature biotechnology2013
High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.
Article in Nature biotechnology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 819 papers, 1 of them a synthesis that pooled it.
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Who cites it
819 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- CRISPR/Cas9-mediated editing of theGM crops & food · 2026Article
- Article
- Single-cell and in vivo profiling reveal heterogeneous and organ-specific CRISPR-Cas9 off-target and translocation outcomes.Nature communications · 2026Article
- Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026Article
- Upper bound on the mutational burden imposed by a CRISPR-Cas9 gene-drive element.G3 (Bethesda, Md.) · 2026Article
- Development of Knockout Cardiac Muscle Cell Lines Using Integrase-Deficient Lentivirus-Mediated CRISPR/Cas9 Gene Editing.Biochemical genetics · 2026Article
- SNIPSNP: precision design of CRISPR/Cas9 knock-in reagents for variant correction and disease modeling.Nucleic acids research · 2026Article
- High-throughput evaluation of in vitro CRISPR activities enables optimized large-scale multiplex enrichment of rare variants.Nature biomedical engineering · 2026Article
- iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.Nature communications · 2026Article
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Engineering a compact high-fidelity Staphylococcus aureus Cas9 variant with broader targeting range and mechanistic insights into its activation.Nature communications · 2026Article
- Advancing regenerative medicine with RNA nanotechnology for chronic and end organ diseases.Communications medicine · 2026Review
- Genome editing across Dictyostelia species enables comparative functional genetics of social amoebas.Scientific reports · 2026Article
- Mismatch tolerance of a gRNA for CRISPR-based gene activation confers broad activity critical for cell reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects.Genome biology · 2026Article
- Assessing off-target effects in CRISPR/Cas9: challenges and strategies for precision DNA editing.Archives of microbiology · 2026Review
- Off-target detection of CRISPR-Cas9 nucleaseSynthetic biology (Oxford, England) · 2026Article
- Physical stimuli-responsive CRISPR-Cas9 systems for spatiotemporally precise control of genome engineering.Theranostics · 2026Review
- Gene therapy for non-obstructive azoospermia: therapeutic avenues and translational pathway to clinical application.Frontiers in genome editing · 2026Review
759 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
The RNA-programmable Cas9 endonuclease cleaves double-stranded DNA at sites complementary to a 20-base-pair guide RNA. The Cas9 system has been used to modify genomes in multiple cells and organisms, demonstrating its potential as a facile genome-engineering tool. We used in vitro selection and high-throughput sequencing to determine the propensity of eight guide-RNA:Cas9 complexes to cleave each of 10(12) potential off-target DNA sequences. The selection results predicted five off-target sites in the human genome that were confirmed to undergo genome cleavage in HEK293T cells upon expression of one of two guide-RNA:Cas9 complexes. In contrast to previous models, our results show that guide-RNA:Cas9 specificity extends past a 7- to 12-base-pair seed sequence. Our results also suggest a tradeoff between activity and specificity both in vitro and in cells as a shorter, less-active guide RNA is more specific than a longer, more-active guide RNA. High concentrations of guide-RNA:Cas9 complexes can cleave off-target sites containing mutations near or within the PAM that are not cleaved when enzyme concentrations are limiting.
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