Utilization of Glucocorticoids as Additives for Enhanced Sialylation of Fc-fusion Protein in CHO Cell Cultures

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 protein...

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Bibliographic Details
Published in:Biotechnology and bioprocess engineering 2021, 26(2), , pp.286-293
Main Authors: Han, Hye-Jin, Lim, Jin-Hyuk, Cha, Hyun-Myoung, Lee, Ji-Hun, Kim, Dong-Il
Format: Article
Language:English
Subjects:
Acids
Additives
Biotechnology
Cell culture
Cell fusion
Chemistry
Chemistry and Materials Science
Corticosterone
Fc receptors
Fusion protein
Glucocorticoids
Glycan
Glycoproteins
Inactivation
Industrial and Production Engineering
Intracellular
Oligosaccharides
Pharmacokinetics
Proteins
Quality management
Research Paper
Sialic acids
생물공학
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Summary: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.
ISSN:1226-8372
1976-3816
DOI:10.1007/s12257-020-0125-3