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Computational and structural biotechnology journal
2022;20 5076-5084.

The application of genome-wide CRISPR-Cas9 screens to dissect the molecular mechanisms of toxins.

Bei Wang, Jun-Zhu Chen, Xue-Qun Luo, Guo-Hui Wan, Yan-Lai Tang, Qiao-Ping Wang
Author Information
  1. Bei Wang: Lab of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, PR China.
  2. Jun-Zhu Chen: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, PR China.
  3. Xue-Qun Luo: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, PR China.
  4. Guo-Hui Wan: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, PR China.
  5. Yan-Lai Tang: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, PR China.
  6. Qiao-Ping Wang: Lab of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, PR China.
PMID: 36187925 DOI: 10.1016/j.csbj.2022.09.012

Abstract

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

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Created with Highcharts 10.0.0CRISPRtoxinsCRISPR-Cas9molecularmechanismsgenome-widescreensscreentoxinBaseEditorGeCKOKnockoutGenome-wideManylife-threateninganimalshumansHoweverspecificantidotesavailableunderlyingtoxicologywell-knownyetfullycharacterizedRecentlyadvancetechnologiesgreatlyacceleratedprocessrevealingtoxiccommonhostsperspectivehigh-throughputmadefeasibleuntanglecomplicatedinteractionsparticularcorrespondingtargetingtissuesreviewpresentoverviewrecentadvancesdissectiontoxins'cytotoxicityusingsummarizecomponentsessentialtoxin-specificproposenewstrategiesfutureresearchapplicationdissectAAPCCAmericanAssociationPoisonControlCentersABEAdenineBacterialCBECytosineCISRPRClusteredRegularlyInterspacedShortPalindromicRepeatsCRISPRaactivationCRISPRiinterferenceDSBDouble-StrandBreakGOFGain-of-functionPooledLibraryLOFLoss-of-functionMAGeCKModel-basedAnalysisMechanismMycotoxinNGSNext-GenerationSequencingNHEJNon-HomologousEndJoiningToxicantToxinVenomsgRNAsingleguideRNA

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