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Comparative proteomic analysis of three Chinese hamster ovary (CHO) host cells

Author:
Xu, Ningning, Ma, Chao, Ou, Jianfa, Sun, Wanqi Wendy, Zhou, Lufang, Hu, Hui, Liu, Xiaoguang Margaret
Source:
Biochemical engineering journal 2017 v.124 pp. 122-129
ISSN:
1369-703X
Subject:
Chinese hamsters, animal ovary, biopharmaceutical industry, biopharmaceuticals, cell engineering, cell growth, dihydrofolate reductase, genes, glycolysis, glycosylation, liquid chromatography, mass spectrometry, proteins, proteomics, translation (genetics), tricarboxylic acid cycle
Abstract:
Chinese hamster ovary (CHO)¹1CHO: Chinese hamster ovary, DHFR: dihydrofolate reductase, LC–MS/MS: Liquid chromatography tandem–mass spectrometry cells have been widely used to express heterologous genes and produce therapeutic proteins in biopharmaceutical industry. Different CHO host cells have distinct cell growth rates and protein expression characteristics. In this study, the expression of about 1307 host proteins in three sublines, i.e. CHO K1, CHO S and CHO/dihydrofolate reductase (dhfr)⁻, were investigated and compared using proteomic analysis. The proteins involved in cell growth, glycolysis, tricarboxylic acid cycle, transcription, translation and glycosylation were quantitated using Liquid chromatography tandem-mass spectrometry (LC–MS/MS). The key host cell proteins that regulate the kinetics of cell growth and the magnitude of protein expression levels were identified. Furthermore, several rational cell engineering strategies on how to combine the desired features of fast cell growth and efficient production of therapeutic proteins into one new super CHO host cell have been proposed.
Agid:
5692151