Many toxins are life-threatening to both animals and humans. However, specific antidotes are not available for most of those toxins. The molecular mechanisms underlying the toxicology of well-known toxins are not yet fully characterized. Recently, the advance in CRISPR-Cas9 technologies has greatly accelerated the process of revealing the toxic mechanisms of some common toxins on hosts from a genome-wide perspective. The high-throughput CRISPR screen has made it feasible to untangle complicated interactions between a particular toxin and its corresponding targeting tissue(s). In this review, we present an overview of recent advances in molecular dissection of toxins' cytotoxicity by using genome-wide CRISPR screens, summarize the components essential for toxin-specific CRISPR screens, and propose new strategies for future research.
Keywords: AAPCC, American Association of Poison Control Centers; ABE, Adenine Base Editor; Bacterial toxin; CBE, Cytosine Base Editor; CISRPR; CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-Cas9 screen; CRISPRa, CRISPR activation; CRISPRi, CRISPR interference; DSB, Double-Strand Break; GOF, Gain-of-function; GeCKO; GeCKO, CRISPR Knockout Pooled Library; Genome-wide; LOF, Loss-of-function; MAGeCK, Model-based Analysis of Genome-wide CRISPR-Cas9 Knockout; Mechanism; Mycotoxin; NGS, Next-Generation Sequencing; NHEJ, Non-Homologous End Joining; Toxicant; Toxin; Venom; sgRNA, single guide RNA.
© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.