In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation.

ABSTRACT: Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat mouse models of diabetes, muscular dystrophy, an

SUBMITTER: Liao HK 

PROVIDER: S-EPMC5732045 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature