ArticleNucleic acids research2024
CRISPR-Cas12a exhibits metal-dependent specificity switching.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.Nature communications · 2026Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- RNA-triggered cell killing with CRISPR-Cas12a2.Nature · 2026Article
- Molecular engineering of CRISPR/Cas12a: from activity enhancement to exponential signal amplification.Chemical science · 2026Review
- SDS-CRISPR for Single-Nucleotide Variant Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA-guided CRISPR-Cas12a effectors for programmable RNA recognition and cleavage.Nature biotechnology · 2026Article
- crRNA Truncation MinimizesJACS Au · 2026Article
- crRNA scaffold remodeling controls CRISPR-Cas12a activity for enhanced performance.Nucleic acids research · 2026Article
- Rapid and ultrasensitive detection ofFrontiers in cellular and infection microbiology · 2026Article
- Loop engineering of AtCas9 for effective and broad genome editing.Cell insight · 2025Article
- Amplification-free cancer diagnosis based on inhibition of Cas12a activity by site-specific 5mC-modified cfDNA.Nucleic acids research · 2025Article
- Tailoring Cas12a functionality with a user-friendly and versatile crRNA variant toolbox.Nature communications · 2025Article
- Rapid CRISPR-Cas9 target-strand nicking can provide phage resistance by reducing DNA abundance.Nucleic acids research · 2025Article
- A Cryptic Binding Pocket Regulates the Metal-Dependent Activity of Cas9.bioRxiv : the preprint server for biology · 2025Article
- Recent advances in CRISPR-based single-nucleotide fidelity diagnostics.Communications medicine · 2025Review
- Direct repeat region 3' end modifications regulate Cas12a activity and expand its applications.Nucleic acids research · 2025Article
- Analysis of metal-dependent DNA nicking activities by Cas endonucleases.Methods in enzymology · 2025Article
- Cas12a domain flexibility guides R-loop formation and forces RuvC resetting.Molecular cell · 2024Article
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Abstract
Cas12a is the immune effector of type V-A CRISPR-Cas systems and has been co-opted for genome editing and other biotechnology tools. The specificity of Cas12a has been the subject of extensive investigation both in vitro and in genome editing experiments. However, in vitro studies have often been performed at high magnesium ion concentrations that are inconsistent with the free Mg2+ concentrations that would be present in cells. By profiling the specificity of Cas12a orthologs at a range of Mg2+ concentrations, we find that Cas12a switches its specificity depending on metal ion concentration. Lowering Mg2+ concentration decreases cleavage defects caused by seed mismatches, while increasing the defects caused by PAM-distal mismatches. We show that Cas12a can bind seed mutant targets more rapidly at low Mg2+ concentrations, resulting in faster cleavage. In contrast, PAM-distal mismatches cause substantial defects in cleavage following formation of the Cas12a-target complex at low Mg2+ concentrations. We observe differences in Cas12a specificity switching between three orthologs that results in variations in the routes of phage escape from Cas12a-mediated immunity. Overall, our results reveal the importance of physiological metal ion conditions on the specificity of Cas effectors that are used in different cellular environments.
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