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KMID : 1094720210260020286
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Biotechnology and Bioprocess Engineering
2021 Volume.26 No. 2 p.286 ~ p.293
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Utilization of Glucocorticoids as Additives for Enhanced Sialylation of Fc-fusion Protein in CHO Cell Cultures
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Han Hye-Jin
Lim Jin-Hyuk
Cha Hyun-Myoung
Lee Ji-Hun
Kim Dong-Il
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Abstract
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Sialylation, which is considered as a critical quality attribute, plays important roles in pharmacokinetics of recombinant proteins. Terminal sialic acids of glycoproteins are modulated by intracellular sialyltransferase (ST) and extracellular sialidase. Since CHO cells producing recombinant proteins can only transfer α2,3-sialic acid to a nascent oligosaccharide, inactivation of α2,6-ST results in a different composition of glycan with human proteins, which have predominantly α2,6-linkages. To overcome this problem and maximize total sialic acid contents, we used glucocorticoids (GCs) that are classified as a steroid hormone in CHO cells expressing both α2,3-ST and α2,6-ST. This study was performed to determine the effect of GCs on CHO cell cultures and sialylation of Fc-fusion protein. We observed that all cultures supplemented with GCs reduced the titer of the Fc-fusion protein, but enhanced the sialylation level, when compared to those of control. Especially, addition of corticosterone increases the levels of α2,6-sialylation as well as the total contents of sialic acid. Enhanced sialic acid contents are thought to be due to the intracellular improvement by sialylatransferase and the inhibition of sialidase. In conclusion, GCs can be utilized as an effective medium additive to improve the quality of biopharmaceuticals using CHO cell cultures.
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KEYWORD
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Chinese hamster ovary cell culture, corticosterone, Fc-fusion protein, glucocorticoids, sialylation
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