Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes

Jasper Edgar Neggers; Bert Kwanten; Tim Dierckx; Hiroki Noguchi; Arnout Voet; Lotte Bral; Kristien Minner; Bob Massant; Nicolas Kint; Michel Delforge; Thomas Vercruysse; Erkan Baloglu; William Senapedis; Maarten Jacquemyn; Dirk Daelemans

doi:10.1038/s41467-017-02349-8

Nature Communications (Feb 2018)

Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes

Jasper Edgar Neggers,
Bert Kwanten,
Tim Dierckx,
Hiroki Noguchi,
Arnout Voet,
Lotte Bral,
Kristien Minner,
Bob Massant,
Nicolas Kint,
Michel Delforge,
Thomas Vercruysse,
Erkan Baloglu,
William Senapedis,
Maarten Jacquemyn,
Dirk Daelemans

Affiliations

Jasper Edgar Neggers: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Bert Kwanten: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Tim Dierckx: KU Leuven Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research
Hiroki Noguchi: KU Leuven Department of Chemistry, Biochemistry Molecular and Structural Biology Section
Arnout Voet: KU Leuven Department of Chemistry, Biochemistry Molecular and Structural Biology Section
Lotte Bral: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Kristien Minner: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Bob Massant: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Nicolas Kint: Department of Hematology, University Hospital Leuven
Michel Delforge: Department of Hematology, University Hospital Leuven
Thomas Vercruysse: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Erkan Baloglu: Karyopharm Therapeutics Inc
William Senapedis: Karyopharm Therapeutics Inc
Maarten Jacquemyn: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research
Dirk Daelemans: KU Leuven Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research

DOI: https://doi.org/10.1038/s41467-017-02349-8
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 14

Abstract

Read online

Cancer therapy drugs are designed to target genetic vulnerabilities, but loss-of-function screens often fail to identify essential genes in drug mechanism studies. Here the authors demonstrate CRISPRres, which exploits in-frame variation generated by indel formation to discover gene-drug interactions.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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