Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs.

ABSTRACT: A lack of tools to precisely control gene expression has limited our ability to evaluate relationships between expression levels and phenotypes. Here, we describe an approach to titrate expression of human genes using CRISPR interference and series of single-guide RNAs (sgRNAs) with systematically modulated activities. We used large-scale measurements across multiple cell models to characterize activities of sgRNAs containing mismatches to their target sites and derived rules governing mismatched sgRNA activity using deep learning. These rules enabled us to synthesize a compact sgRNA library to titrate expression of ~2,400 genes essential for robust cell growth and to construct an in silico sgRNA library spanning the human genome. Staging cells along a continuum of gene expression levels c

SUBMITTER: Jost M 

PROVIDER: S-EPMC7065968 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature