Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform.

ABSTRACT: Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. W

SUBMITTER: Zhao J 

PROVIDER: S-EPMC9615120 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature