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Cited by 88CRISPR and Genetic EngineeringComputational Drug Discovery MethodsProtein Degradation and Inhibitors

CRISPR Approaches to Small Molecule Target Identification

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Jost, Marco, Weissman, Jonathan S.·2018·ACS Chemical Biology
DOI 10.1021/acschembio.7b00965PMC PMC5834945
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Abstract

A long-standing challenge in drug development is the identification of the mechanisms of action of small molecules with therapeutic potential. A number of methods have been developed to address this challenge, each with inherent strengths and limitations. We here provide a brief review of these methods with a focus on chemical-genetic methods that are based on systematically profiling the effects of genetic perturbations on drug sensitivity. In particular, application of these methods to mammalian systems has been facilitated by the recent advent of CRISPR-based approaches, which enable one to readily repress, induce, or delete a given gene and determine the resulting effects on drug sensitivity.

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  • In human immortalized 2D cell lines, large-scale CRISPR-based genetic screens have yielded significant insights into normal and disease biology and serve as an unbiased method for investigating disease mechanisms and gene-drug interactions.

    “In human immortalized 2D cell lines, large-scale CRISPR-based genetic screens have yielded significant insights into both normal and disease biology, serving as an unbiased method for investigating disease mechanisms and gene-drug interactions7,8.”

    From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [8]

    The ‘Functional genomics tools for chemical-genetic screens in human cells’ section describes genome-wide pooled CRISPR screens that identify genes required for growth and genetic dependencies of drugs. It does not specify immortalized 2D cell lines or establish the broader claim that these screens have yielded insights into both normal and disease biology. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Jost, M., & Weissman, J. S.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
  • Jost, Marco
  • Weissman, Jonathan S.
ORCID
Venue
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Published
2018-01-25
Volume
13
Issue
2
Pages
366-375
ISSN
  • 1554-8929 (ISSN-L)
  • 1554-8937
DOI
10.1021/acschembio.7b00965
PMC
PMC5834945
OpenAlex
W2780930919
Cited by
88
References
19
Citations by year
2026: 5 · 2025: 7 · 2024: 12 · 2023: 7 · 2022: 20 · 2021: 12 · 2020: 14 · 2019: 5 · 2018: 6
FWCI
0.67
Type
journal article
Language
en
Open access
Locations
  • ACS Chemical Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • U.S. Department of Health and Human Services (U01 CA168370, R01 DA036858, F32 GM116331, P50 GM102706)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
CRISPR, small molecule target identification, mechanism of action, chemical genetics, drug sensitivity profiling, gene perturbation, gene repression, gene induction, gene deletion, drug development
MeSH terms
Gene Editing, Animals, Humans, Saccharomyces cerevisiae, Clinical Laboratory Techniques, Genomics, Drug Discovery, CRISPR-Cas Systems, CRISPR-Associated Proteins

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