Cytosolic miRNA-Inducible Nuclear Translocation of CRISPR Protein for Disease-Specific Genome Modification

Abstract

Inspired by the intrinsic nature of microRNA-mediated mRNA cleavage, we developed a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate translocation of proteins. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs. Using the endogenous mRNA decay mechanism, our platform is able to remodel a cell's natural biology to allow the entry of precise drugs into the nucleus, devoid of non-specific translocation. This strategy is promising for applications in which the reaction must be controlled via intracellular stimuli and modulates Cas9 proteins to ensure safe genome modification in diseased conditions.