miR-Cabiner: A Universal microRNA Sensing Platform\nBased on Self-Stacking Cascaded Bicyclic DNA Circuit-Mediated CRISPR/Cas12a

CRISPR/Cas12a-based\ndiagnostics have great potential for sensing\nnucleic acids, but their application is limited by the sequence-dependent\nproperty. A platform termed miR-Cabiner (a universal <u>miR</u>NA sensing platform based on self-stacking <u>ca</u>scaded <u>bi</u>cyclic D<u>N</u>A\ncircuit-m<u>e</u>diated C<u>R</u>ISPR/Cas12a)\nis demonstrated herein that is sensitive and universal for analyzing\nmiRNAs. This platform combines catalytic hairpin assembly (CHA) and\nhybrid chain reaction (HCR) into a unified circuit and finally cascades\nto CRISPR/Cas12a. Compared with the CHA–Cas12a and HCR–Cas12a\nsystems, miR-Cabiner exhibits a significantly higher reaction rate.\nPanels of miRNAs (miR-130a, miR-10b, miR-21, and miR-1285), which\nare associated with diagnosis, staging, and prognosis of breast cancer,\nare designed to demonstrate the universality of miR-Cabiner. Four\nmiRNAs can be detected to the fM-level by simply tuning the sequence\nin CHA components. Additionally, miRNA panel analysis also shows high\naccuracy in practical samples. This universally applicable platform\nfor detecting miRNA may serve as an excellent tool for clinical diagnosis.