Enhanced Human-like Sialylation of Fc-fusion Protein in CHO Cell Cultures by Glucocorticoids

초록

Glycosylation is not only a major post-translational modification, but a critical quality attribute in therapeutic glycoprotein. Especially, terminal sialic acid affects pharmacokinetics, and pharmacodynamics of biopharmaceuticals. Chinese hamster ovary (CHO) cells are the most used host for producing therapeutic proteins because of human-like glycosylation. It was demonstrated that human overexpression of α2,6- sialyltransferase (α2,6-ST) gene facilitated the addition of α2,6-sialic acid residue [1]. Glucocorticoids (GCs) which are steroid hormones were reported as enhancing sialylation in CHO cell cultures [2]. In this study, we evaluated the effect of GCs on the quantity and quality of Fc-fusion protein in CHO cells overexpressing α2,6- ST. We added seven types of GCs to culture media at day 0. Supplementation of GCs enhanced cell viability and prevented cell death causing the release of sialidase. Also, it was confirmed that the addition of GCs with overexpression of α2,6-ST triggered more sialylation than control condition. In conclusion, overexpression ofα2,6-ST and supplementation of GCs were found to be a simultaneous and effective method for enhancing the level of α2,6 sialylation in Fc-fusion protein.