ArticleNucleic acids research2025
Proximity-activated guide RNA of CRISPR-Cas12a for programmable diagnostic detection and gene regulation.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Repeat region engineering of Cas13a crRNA enables conformational gating-based autocatalytic CRISPR biosensing.Nucleic acids research · 2026Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- Molecular engineering of CRISPR/Cas12a: from activity enhancement to exponential signal amplification.Chemical science · 2026Review
- Programmable spatiotemporal control of CRISPR-Cas12a: Engineering precision for next-generation gene editing and diagnostics.Synthetic and systems biotechnology · 2026Review
- TopCas: Topology-Gated Cas12a via DNA-RNA Chimeric Circular crRNA for Amplification-Free Nucleic Acid Detection and Conditional Gene Editing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The stimuli-responsive CRISPR-Cas12a system for modulating the selective aggregation of cell membrane receptors.Journal of nanobiotechnology · 2026Article
- MARPLE: A Proximity-Triggered CRISPR-Cas13 Platform for Ultrasensitive Antibody Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recognition, Signal Transduction, and Amplification of Nucleic Acids Under Isothermal Condition.Advanced genetics (Hoboken, N.J.) · 2026Article
- Distinct effects of tea types and components on circadian rhythm entrainment and clock gene regulation.NPJ science of food · 2025Article
- Advancements and Applications of Split Technology in CRISPR/Cas12a: Transforming Molecular Diagnostics and Biosensing.Biosensors · 2025Review
- PAM-free hairpin target binding activates trans-cleavage activity of Cas12a.Nucleic acids research · 2025Article
- Synthetic CRISPR Networks Driven by Transcription Factors via Structure-Switching DNA Translators.Journal of the American Chemical Society · 2025Article
- Ultra-sensitiveFrontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
The flexibility and programmability of CRISPR-Cas technology have made it one of the most popular tools for biomarker diagnostics and gene regulation. Especially, the CRISPR-Cas12 system has shown exceptional clinical diagnosis and gene editing capabilities. Here, we discovered that although the top loop of the 5' handle of guide RNA can undergo central splitting, deactivating CRISPR-Cas12a, the segments can dramatically restore CRISPR function through nucleic acid self-assembly or interactions with small molecules and aptamers. This discovery forms the basis of an engineered Cas12a system with a programmable proximity-activated guide RNA (PARC-Cas12a) that links targets of interest to dsDNA. Leveraging the efficient trans- and cis-cleavage of Cas12, our findings further inspired a detection platform design for RNAs or non-nucleic acid biomarkers, enabling highly sensitive and multiplexed analysis. We further demonstrated the feasibility of RNA-controllable gene knockout/knockdown in Escherichia coli. Notably, we successfully validated the gene regulatory capabilities of the PARC-Cas12a system within mammalian cell systems by utilizing the classical theophylline molecule-aptamer system. Our results introduce a programmable toolbox for precise diagnostics and cell regulation, allowing the development of versatile diagnostic tools, complex synthetic biological circuits, and cellular biosensors.
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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.