Genome-scale functional genomics screening highlights genes impacting protein fucosylation in Chinese hamster ovary cells.

Autor:	Barlan K; Genomics Research Center, North Chicago, IL, United States., Bhide GP; Biologics Analytical Research and Development, Worcester, MA, United States., White DR; Biologics Production, AbbVie, North Chicago, IL, United States., Lake MR; Biologics Production, AbbVie, North Chicago, IL, United States., Lu C; Genomics Research Center, North Chicago, IL, United States., Rieder SE; Biologics Science and Technology, AbbVie Bioresearch Center, Worcester, MA, United States., Fan L; Biologics Science and Technology, AbbVie Bioresearch Center, Worcester, MA, United States., Hsieh CL; Genomics Research Center, North Chicago, IL, United States. Electronic address: chenlin.hsieh@abbvie.com.
Jazyk:	angličtina
Zdroj:	SLAS discovery : advancing life sciences R & D [SLAS Discov] 2024 Jan; Vol. 29 (1), pp. 52-58. Date of Electronic Publication: 2023 Oct 14.
DOI:	10.1016/j.slasd.2023.10.004
Abstrakt:	N-linked glycosylation is a common post-translational modification that has various effects on multiple types of proteins. The extent to which an N-linked glycoprotein is modified and the identity of glycans species involved is of great interest to the biopharmaceutical industry, since glycosylation can impact the efficacy and safety of therapeutic monoclonal antibodies (mAbs). mAbs lacking core fucose, for example, display enhanced clinical efficacy through increased antibody-dependent cellular cytotoxicity. We performed a genome-wide CRISPR knockout screen in Chinese hamster ovary (CHO) cells, the workhorse cell culture system for industrial production of mAbs, aimed at identifying novel regulators of protein fucosylation. Using a lectin binding assay, we identified 224 gene perturbations that significantly alter protein fucosylation, including well-known glycosylation genes. This functional genomics framework could readily be extended and applied to study the genetic pathways involved in regulation of other glycoforms. We hope this resource will provide useful guidance toward the development of next generation CHO cell lines and mAb therapeutics. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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