ArticleNature biotechnology2025
RNA structure modulates Cas13 activity and enables mismatch detection.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed.
- Repeat region engineering of Cas13a crRNA enables conformational gating-based autocatalytic CRISPR biosensing.Nucleic acids research · 2026Article
- CRISPR technologies for detecting DNA and RNA methylation: Mechanisms, platforms, and translational opportunities.Bioengineering & translational medicine · 2026Review
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- A structural accessibility principle for LbuCas13a activation by noncontiguous DNA.Nucleic acids research · 2026Article
- Cas-regulation-targeting chimera enables selective and tunable control of CRISPR/Cas12a.Nucleic acids research · 2026Article
- Intersegmental transfers drive target search in an RNA-targeting CRISPR system.bioRxiv : the preprint server for biology · 2026Article
- Machine Learning for CRISPR-Based Diagnostics.International journal of molecular sciences · 2026Review
- Towards deployable CRISPR-based nucleic acid detection.Progress in biomedical engineering (Bristol, England) · 2026Review
- Development of a multifunctional nucleic acid response platform utilizing the Cas12a and Cas13a integrated targeting system.Nucleic acids research · 2026Article
- A universal and orthogonal safety valve for CRISPR/Cas12a without chemical modification or external stimulation.Nucleic acids research · 2026Article
- A kinetic approach for mapping seed regions of CRISPR ribonucleoprotein and improving specificity.Nucleic acids research · 2026Article
- Programmable pH-responsive DNA inter-strand matching (PRISM) for precision molecular band-pass actuation.Theranostics · 2026Article
- CRISPR anti-tag-mediated room-temperature RNA detection using CRISPR/Cas13a.Nature communications · 2025Article
- A handheld microfluidic manifold for massively multiplexed CRISPR-based nucleic acid detection.bioRxiv : the preprint server for biology · 2025Article
- A two-step mechanism for RIG-I activation by influenza virus mvRNAs.Science advances · 2025Article
- Recent advances in CRISPR-based single-nucleotide fidelity diagnostics.Communications medicine · 2025Review
- Quantification of influenza virus mini viral RNAs using Cas13.RNA (New York, N.Y.) · 2024Article
- Genetic manipulation of bacteriophage T4 utilizing the CRISPR-Cas13b system.Frontiers in genome editing · 2024Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Cas13 is activated by the hybridization of a CRISPR RNA to a complementary single-stranded RNA protospacer in a target RNA. While Cas13 is not activated by double-stranded RNA in vitro, it robustly targets RNA in cellular environments where RNAs are highly structured. The mechanism by which Cas13 targets structured RNAs remains unknown. Here, we systematically probe the effects of secondary structure on Cas13. We find that secondary structure in the protospacer and 3' to it inhibits Cas13 activity and quantitatively explains the former effect through a strand displacement framework. We then harness strand displacement to generate an 'occluded' Cas13, which enhances mismatch discrimination up to 50-fold and enables sequence-agnostic mutation identification at low (<1%) allele frequencies. Using occluded Cas13, we identify human-adaptive mutations in SARS-CoV-2 and human and avian influenza A viruses, as well as oncogenic mutations in KRAS. Our work leverages improved mechanistic understanding of Cas13 to expand the scope of RNA diagnostics and enable structure-informed Cas13 approaches.
Identifiers
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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.