Conformationally Locked Peptide-DNA Nanostructures for CRISPR-Amplified Activity-Based Sensing.

ABSTRACT: We introduce a new class of chemical probes for activity-based sensing of proteases, termed cleavable, locked initiator probes (CLIPs). CLIPs contain a protease-cleavable peptide linked between two programmable DNA strands-an "initiator" DNA and a shorter "blocking" DNA. These DNA sequences are designed to hybridize, creating a "locked" hairpin-like structure. Upon proteolytic cleavage, the initiator strand is released, triggering the activation of CRISPR-Cas12a enzymes and producing an amplified fluorescence response. CLIPs generate more than 20-fold turn-on signals at room temperature (25 °C), significantly outperforming commercial probes by yielding ∼40-fold lower limits of detection (LOD) at 100-fold lower concentrations. Their versatility enables the detection of various disease-relev

SUBMITTER: Snider DM 

PROVIDER: S-EPMC12171325 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature