SHIN Cheol-Hee Park, Su Chan Park, Il-Geun Kim, Hyerim An, Byoungha Lee Choong Il Kim, Sang-Heon Lee, Juyong Lee, Ji Min Oh, Seung Ja 2024-01-19T12:01:11Z 2024-01-19T12:01:11Z 2022-06-17 2022-06 0305-1048 https://pubs.kist.re.kr/handle/201004/115145 MicroRNA-dependent mRNA decay plays an important role in gene silencing by facilitating posttranscriptional and translational repression. Inspired by this intrinsic nature of microRNA-mediated mRNA cleavage, here, we describe a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate the translocation of proteins. We applied the mRNA bridge mimetics platform to Cas9 protein to confer it the ability to translocate into the nucleus via cleavage of the nuclear export signal. This system performed programmed gene editing in vitro and in vivo. Combinatorial treatment with cisplatin and miR-21-EZH2 axis-targeting CRISPR Self Check-In improved sensitivity to chemotherapeutic drugs in vivo. Using the endogenous microRNA-mediated 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. The mRNA bridge mimetics 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. English Oxford University Press Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification Article 10.1093/nar/gkac431 1 Nucleic Acids Research, v.50, no.10, pp.5919 - 5933 Nucleic Acids Research 50 10 5919 5933 Y scie scopus 000805319200001 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article CANCER CELLS RNA EXPRESSION BINDING OVEREXPRESSION TARGETS