ArticleCell2024
Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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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.
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Who cites it
41 citing papers in PubMed.
- A dynamically frustrated allosteric checkpoint consistent with conformational proofreading in CRISPR-Cas9.Nucleic acids research · 2026Article
- Stepwise DNA-unwinding gates TnpB genome-editing activity.Molecular cell · 2026Article
- Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.Nature communications · 2026Article
- Gene Editing-Driven Engineering of Microbial Systems and Metabolites for Precision Medicine and Sustainable Environmental Remediation.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Article
- Structural basis of AtCas9 recognition of PAM mutants in underwound DNA topology.Nature structural & molecular biology · 2026Article
- Biophysical characterization ofSensors & diagnostics · 2026Article
- Selective Elimination of TP53 Mutant Cells by Transcript-Activated Chromatin Shredding.bioRxiv : the preprint server for biology · 2026Article
- Article
- Engineering a compact high-fidelity Staphylococcus aureus Cas9 variant with broader targeting range and mechanistic insights into its activation.Nature communications · 2026Article
- Structural insight into IscB's RNA-lid-based inactivation mechanism.Nature structural & molecular biology · 2026Article
- Advances in Double-Stranded DNA Targeting Technologies.Exploration (Beijing, China) · 2026Review
- Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026Article
- Specificity of DNA targeting by RNA-guided pAgo nucleases.Nucleic acids research · 2026Article
- Multiplex Gene Editing and Effect Analysis of Yield, Fragrance, and Blast Resistance Genes in Rice.Genes · 2026Article
- Stepwise DNA unwinding gates TnpB genome-editing activity.bioRxiv : the preprint server for biology · 2026Article
- A review of recent studies on CRISPR/Cas9-mediated genome editing in a variety of muscle-related genetic disorders.Journal of translational medicine · 2025Review
- Loop engineering of AtCas9 for effective and broad genome editing.Cell insight · 2025Article
- Structural and functional insights into internal domain replacement in SpCas9 for protein engineering.Scientific reports · 2025Article
Corrections and comments
- Update of
Authors and funding
10 authors.
Funding
Abstract
Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels. Cryoelectron microscopy (cryo-EM) structures of the wild-type and improved GeoCas9 (iGeoCas9) enzymes reveal extended contacts between the WED domain of iGeoCas9 and DNA substrates. Biochemical analysis shows that iGeoCas9 accelerates DNA unwinding to capture substrates under the magnesium-restricted conditions typical of mammalian but not bacterial cells. These findings enabled rational engineering of other Cas9 orthologs to enhance genome-editing levels, pointing to a general strategy for editing enzyme improvement. Together, these results uncover a new role for the Cas9 WED domain in DNA unwinding and demonstrate how accelerated target unwinding dramatically improves Cas9-induced genome-editing activity.
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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.