Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics

Abstract

Pathogenic xenobiotics are ubiquitous in the environment. Environmental carcinogens induce mutations leading to tumors; pathogens relying on environmental media transmission cause infections; exposure to chemical or biological pollutants triggers toxicant poisoning. The mechanisms of xenobiotics work by abnormal expression of genes. Since their inception, genome-wide CRISPR/Cas9 knockout libraries have been rapidly applied in vitro to dissect the mechanism of diseases. Genome-wide screening of CRISPR/Cas9 knockout libraries has helped to identify genes essential for tumor survival, combinations of genes for synthetic lethal effects, and genes associated with drug resistance or susceptibility. In addition, key host factors and complex toxicological mechanisms of viral infection have been elucidated, contributing to the development of antidotes and the reduction of the incidence of adverse effects. CRISPR/Cas9 library screening can be combined with single-cell sequencing and organoid technologies to identify novel gene interactions and more reliable preclinical data. Future trends in such screening aim to identify more potential molecular targets for more exogenous pathogenic factors, combine screening with other emerging technologies to expand its use in in vitro models, and develop more accurate, accessible, and cost-effective genome editing tools.