ArticleScience advances2024
High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Machine-learning in optimization of CRISPR technology.Machine learning. Health · 2026Review
- CRISPR RNA architecture steers Cas9 catalysis and fidelity via a guide repeat clasp motif.Nucleic acids research · 2026Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- Article
- Computation and deep-learning-driven advances in CRISPR genome editing.Nature structural & molecular biology · 2026Review
- Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC.ACS omega · 2025Review
- Design Rules for Expanding PAM Compatibility in CRISPR-Cas9 from the VQR, VRER and EQR variants.bioRxiv : the preprint server for biology · 2025Article
- A Cryptic Binding Pocket Regulates the Metal-Dependent Activity of Cas9.bioRxiv : the preprint server for biology · 2025Article
- Graph Attention Neural Networks Reveal TnsC Filament Assembly in a CRISPR-Associated Transposon.bioRxiv : the preprint server for biology · 2025Article
- Article
- Advancing Molecular Simulations: Merging Physical Models, Experiments, and AI to Tackle Multiscale Complexity.The journal of physical chemistry letters · 2025Review
- Unveiling Cas8 dynamics and regulation within a transposon-encoded Cascade-TniQ complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dynamic sampling of a surveillance state enables DNA proofreading by Cas9.Cell chemical biology · 2025Article
- Article
- Muscle-specific gene editing improves molecular and phenotypic defects in a mouse model of myotonic dystrophy type 1.Clinical and translational medicine · 2025Article
- Flexibility in PAM Recognition Expands DNA Targeting in xCas9.bioRxiv : the preprint server for biology · 2025Article
- CRISPR-dependent base editing as a therapeutic strategy for rare monogenic disorders.Frontiers in genome editing · 2025Review
- Graph theory approaches for molecular dynamics simulations.Quarterly reviews of biophysics · 2024Article
- Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The high-fidelity (HF1), hyper-accurate (Hypa), and evolved (Evo) variants of the CRISPR-associated protein 9 (Cas9) endonuclease are critical tools to mitigate off-target effects in the application of CRISPR-Cas9 technology. The mechanisms by which mutations in recognition subdomain 3 (Rec3) mediate specificity in these variants are poorly understood. Here, solution nuclear magnetic resonance and molecular dynamics simulations establish the structural and dynamic effects of high-specificity mutations in Rec3, and how they propagate the allosteric signal of Cas9. We reveal conserved structural changes and dynamic differences at regions of Rec3 that interface with the RNA:DNA hybrid, transducing chemical signals from Rec3 to the catalytic His-Asn-His (HNH) domain. The variants remodel the communication sourcing from the Rec3 α helix 37, previously shown to sense target DNA complementarity, either directly or allosterically. This mechanism increases communication between the DNA mismatch recognition helix and the HNH active site, shedding light on the structure and dynamics underlying Cas9 specificity and providing insight for future engineering principles.
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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.