文献类型：期刊文献

英文题名：Ultra-low carbon dioxide partial pressure improves the galactosylation of a monoclonal antibody produced in Chinese hamster ovary cells in a bioreactor

作者：Wang, Chen[1];Wang, Jiaqi[1];Chen, Min[2];Fan, Li[1];Zhao, Liang[1];Tan, Wen-Song[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Bioengine Biotechnol Co Ltd, Shanghai 200237, Peoples R China

年份：2018

卷号：40

期号：8

起止页码：1201

外文期刊名：BIOTECHNOLOGY LETTERS

收录：;EI(收录号：20182605360814);WOS:【SCI-EXPANDED(收录号:WOS:000438090800005)】；

基金：This work was supported by the National Natural Science Foundation of China (Nos. 21406066, 21106045), the National High Technology Research and Development Program of China (863 Program) (No. 2012AA02A303), the Fundamental Research Funds for the Central Universities (No. 22221818014), and the Development Funds of Shanghai Zhangjiang National Independent Innovation Demonstration Zone (No. ZJ2015-ZD-002).

语种：英文

外文关键词：Chinese hamster ovary cell; Glycosylation; pCO(2); Scale-up; Monoclonal antibody

摘要：To explore the influence of ultra-low carbon dioxide partial pressure (pCO(2)) on the monoclonal antibody (mAb) N-glycosylation profile in Chinese hamster ovary (CHO) cell culture. In fed-batch bioreactor cultures, lowering the pCO(2) in the medium (< 25 mmHg) via increasing headspace aeration decreased the cell viability and mAb production in CHO cells. Additionally, mAb galactosylation under low pCO(2) was approximately 27.45 +/- 2.13%, noticeably higher than that observed under normal pCO(2) (21.36 +/- 1.66%) at harvest. However, all of the relevant intracellular nucleotide sugar concentrations were dramatically decreased to approximately 50% of the levels found under normal pCO(2) on day 7. Real-time PCR revealed that the upregulation of galactosylation-related glycosyltransferase genes and substrate transporter genes played a critical role in the improved galactosylation under the ultra-low pCO(2) condition. In the bioreactor culture processes, ultra-low pCO(2) demonstrated a positive effect on mAb galactosylation.