Combinatorial genetics in liver repopulation and carcinogenesis with a in vivo CRISPR activation platform.

ABSTRACT: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 activation (CRISPRa) systems have enabled genetic screens in cultured cell lines to discover and characterize drivers and inhibitors of cancer cell growth. We adapted this system for use in vivo to assess whether modulating endogenous gene expression levels can result in functional outcomes in the native environment of the liver. We engineered the catalytically dead CRISPR-associated 9 (dCas9)-positive mouse, cyclization recombination-inducible (Cre) CRISPRa system for cell type-specific gene activation in vivo. We tested the capacity for genetic screening in live animals by applying CRISPRa in a clinically relevant model of liver injury and repopulation. We targeted promoters of interest in regenerating

SUBMITTER: Wangensteen KJ 

PROVIDER: S-EPMC5930141 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature