ArticleCell2022
Structural basis for Cas9 off-target activity.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Pooled it
- Cas10 residues lining the target RNA binding channel regulate interference by distinguishing cognate target RNA from mismatched targets.RNA biology · 2026Article
- Structural basis for target discrimination and activation by Cas13d.Science advances · 2026Article
- On-target and off-target activities of CRISPR therapeutics across scales.Trends in biotechnology · 2026Review
- CRISPR RNA architecture steers Cas9 catalysis and fidelity via a guide repeat clasp motif.Nucleic acids research · 2026Article
- Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- Modeling Tay-Sachs Disease in Astrocyte-like Cells Reveals Significant Changes in the Transcriptomic Profile.International journal of molecular sciences · 2026Article
- Molecular basis of single-mismatch-induced nuclease-to-nickase conversion in TIGR-TasH.Nucleic acids research · 2026Article
- Efficient gene disruption with CRISPR-Cas3 in human T cells.NAR cancer · 2026Article
- Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems.Biotechnology journal · 2026Review
- 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination.Science advances · 2026Article
- Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Nature communications · 2026Article
- TKC-MC: An Effective Strategy for Generating Heritable Heterozygous Mutations in Essential Genes in Rice.Plant biotechnology journal · 2026Article
- Testicular mRNA-LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CrisprPr: a hybrid-driven framework for CRISPR/Cas9 off-target prediction with analysis of prior-information updates.Briefings in bioinformatics · 2026Article
- A Programmable Eukaryotic Argonaute Nuclease with Dual DNA and RNA Cleavage Activity from Thermophilic FungusSmall science · 2026Article
- Integrase-On-Demand: bioprospecting integrases for targeted genomic insertion of genetic cargo.Nucleic acids research · 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
73 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
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The target DNA specificity of the CRISPR-associated genome editor nuclease Cas9 is determined by complementarity to a 20-nucleotide segment in its guide RNA. However, Cas9 can bind and cleave partially complementary off-target sequences, which raises safety concerns for its use in clinical applications. Here, we report crystallographic structures of Cas9 bound to bona fide off-target substrates, revealing that off-target binding is enabled by a range of noncanonical base-pairing interactions within the guide:off-target heteroduplex. Off-target substrates containing single-nucleotide deletions relative to the guide RNA are accommodated by base skipping or multiple noncanonical base pairs rather than RNA bulge formation. Finally, PAM-distal mismatches result in duplex unpairing and induce a conformational change in the Cas9 REC lobe that perturbs its conformational activation. Together, these insights provide a structural rationale for the off-target activity of Cas9 and contribute to the improved rational design of guide RNAs and off-target prediction algorithms.
Indexed as
Identifiers
What OpenQuestion holds
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.