ArticleSignal transduction and targeted therapy2025
Molecular insights and rational engineering of a compact CRISPR-Cas effector Cas12h1 with a broad-spectrum PAM.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The Single-Stranded DNA Platform: A Potential Broad-Spectrum Vector for Editing Genes in Prokaryotes: ssDNA May Break Through the Difficulties of Genetic Manipulation on Non-Model Bacteria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- AI-Predicted Model-Guided Rebuilding of the Experimental Structure of Mouse δ-Aminolevulinic Acid Dehydratase.International journal of molecular sciences · 2026Article
- Engineering hypercompact IscB nucleases for efficient and versatile genome editing in rice.Genome biology · 2026Article
- Multilayer regulation of CRISPR systems: integrating anti-CRISPR proteins, CRISPRi/a, and quorum sensing networks.Frontiers in cellular and infection microbiology · 2026Review
- Unlocking mRNA-driven CRISPR-Cas9 gene therapy via optimizing mRNA and the delivery vectors.Molecular therapy. Nucleic acids · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Cas12h1 is a compact CRISPR-associated nuclease from functionally diverse type V CRISPR-Cas effectors and recognizes a purine-rich protospacer adjacent motif (PAM) distinct from that of other type V Cas effectors. Here, we report the nickase preference of Cas12h1, which predominantly cleaves the nontarget strand (NTS) of a double-stranded DNA (dsDNA) substrate. In addition, Cas12h1 acts as a nickase in human cells. We further determined the cryo-EM structures of Cas12h1 in the surveillance, R-loop formation, and interference states, revealing the molecular mechanisms involved in the crRNA maturation, target recognition, R-loop formation, nuclease activation and target degradation. Cas12h1 notably recognizes a broad 5'-DHR-3' PAM (D is A, G, or T; H is A, C, or T; R is A or G) both in vitro and in human cells. In addition, Cas12h1 utilizes a distinct activation mechanism that the lid motif undergoes a "flexible to stable" transition to expose the catalytic site to the substrate. A high-fidelity nucleic acid detector, Cas12h1
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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.