Effect of Sialic Acid on Mammalian Cell Culture and Protein Expression A Potential Productivity Enhancer for Biopharmaceutical Cell Culture Processes

Improved productivity of the two most commonly used cell lines in the biopharmaceutical industry, such as human embryonic kidney 293 (HEK293) and Chinese hamster ovary (CHO), could reduce production costs and increase manufacturing capacity. One method for increasing proteinproductivity is the addition of antioxidants during the cell culture process. In this study, we examined the effect of sialic acid (SA) on one HEK293 cell line and two CHO cell lines. The addition of SA to HEK293 cell led to a higher viable cell density (VCD), viability (Via), and a lower lactate content in the later stage of cultures. Further results showed that SA reduced the reactive oxygen species (ROS), improved cell viability, reduced lactate production, and increased antibody expression by more than 20% in the later stage of the two CHO cell lines cultures. Besides, an optimized dose of SA had no significant effect on acidic variants level aggregation level, N-linked glycosylation pattern, and SA content on antibodies. These results suggest that the addition of SA can improve the productivity of biopharmaceutical cell culture processes.

生物制药行业中两种最常用的细胞系——人胚肾293（human embryonic kidney 293, HEK293）与中国仓鼠卵巢（Chinese hamster ovary, CHO）——的生产效能提升，可降低生产成本并扩大制造产能。提升蛋白生产效能的一种手段是在细胞培养过程中添加抗氧化剂。本研究探究了唾液酸（sialic acid, SA）对一株HEK293细胞系及两株CHO细胞系的作用效果。向HEK293细胞中添加SA，可在培养后期提升活细胞密度（viable cell density, VCD）与细胞活率（viability, Via），并降低乳酸含量。进一步的结果显示，在两株CHO细胞系的培养后期，SA可清除活性氧（reactive oxygen species, ROS）、提升细胞活率、减少乳酸生成，并使抗体表达量提升20%以上。此外，优化剂量的SA对抗体的酸性变体水平、聚集水平、N-连接糖基化（N-linked glycosylation）模式以及抗体结合的唾液酸含量均无显著影响。上述结果表明，添加SA可提升生物制药细胞培养过程的生产效能。