Proximity-activated guide RNA of CRISPR-Cas12a for programmable diagnostic detection and gene regulation.

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 detecti

SUBMITTER: Hu Z 

PROVIDER: S-EPMC11760950 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature