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

时间:2026-05-13 人气:

Author: Chen Wang, Jiaqi Wang, Min Chen, Li Fan, Liang Zhao*, Wen-Song Tan.
Biotechnology Letters, 2018, 40(8): 1201-1208

Abstract
Objective To explore the influence of ultra-low carbon dioxide partial pressure (pCO2) on the monoclonal antibody (mAb) N-glycosylation profile in Chinese hamster ovary (CHO) cell culture. Results In fed-batch bioreactor cultures, lowering the pCO2 in the medium (<25 mmHg) via increasing headspace aeration decreased the cell viability and mAb production in CHO cells. Additionally, mAb galactosylation under low pCO2 was approximately 27.45 ± 2.13%, noticeably higher than that observed under normal pCO2 (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 pCO2 on day 7. Real-time PCR revealed that the upregulation of galactosylationrelated glycosyltransferase genes and substrate transporter genes played a critical role in the improved galactosylation under the ultra-low pCO2 condition. Conclusions In the bioreactor culture processes, ultra-low pCO2 demonstrated a positive effect on mAb galactosylation.

反应器培养CHO细胞生产单抗过程中过低的二氧化碳分压导致抗体半乳糖基化水平升高
目的:研究过低的二氧化碳分压(pCO2)对中国仓鼠卵巢(CHO)细胞培养产生的单克隆抗体N-糖基化的影响。
结果:在反应器流加培养过程中,通过增加表层通气来降低培养基中的 pCO2 (<25 mmHg)这一方式会降低CHO细胞的细胞活力及单抗产量。此外,在过低的pCO2条件下,单抗糖基的半乳糖化为27.45±2.13%,显著高于正常pCO2条件下收获的单抗糖基的半乳糖化水平(21.36±1.66%)。然而,所有相关的胞内核苷糖浓度在第7天均急剧下降到正常pCO2培养条件下的约50%。实时PCR显示,在过低pCO2条件下,与半乳糖基化相关的糖基转移酶基因及底物转运子基因的上调对改善半乳糖基化起着关键作用。
结论:在反应器培养过程中,过低的pCO2会提高单抗N糖链的半乳糖化水平。


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