Abstract
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 protein productivity 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.
Highlights
In the past 30 years, recombinant protein drugs have been widely used to treat various complex diseases [1]
Since sialic acid (SA) is acidic in nature, it is necessary to adjust the pH to 7.0 ± 0.1 with sodium hydroxide when the SA solution is prepared to mitigate the influence of pH changes on the cell culture
We studied the effect of SA on cell culture and protein production
Summary
In the past 30 years, recombinant protein drugs have been widely used to treat various complex diseases [1]. Among the 10 best-selling drugs worldwide in 2020, recombinant protein drugs occupy. Mammalian cells are the preferred host cell for the production of recombinant therapeutic modalities, such as monoclonal antibodies. Mammalian cells can produce post-translationally modified proteins (mainly glycosylated forms) that display modifications similar to those observed in human cells [2]. Several mammalian cell lines are in use for the production of recombinant proteins, including Chinese hamster ovary (CHO) and NS0 cells. 70% of recombinant therapeutic proteins are produced in CHO cells [3,4]. The first step in the production of recombinant protein drugs is the large-scale cell culture; improving the productivity of the cell culture process will increase the manufacturing capacity and reduce the cost of protein drugs
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