Improvement of Albumin-erythropoietin Production by Chemical Chaperone in CHO Cell Cultures

초록

Chinese hamster ovary (CHO) cells are the mostly favored host cell line for the industrial production of recombinant proteins. Chemical chaperones are a class of low molecular weight compounds that are known to reduce ER stress and used to improve protein production, stability and glycosylation. In this study, we identify the effect of several chemical chaperones such as glycerol, dimethyl sulfoxide (DMSO), 4-phenylbutyrate (PBA) on the sialylation of albumin-erythropoietin (Alb-EPO). Cells were subjected to 1% glycerol, 1% DMSO, 1 mM 4-PBA, respectively, at day 0. Viable cell density and viability were reduced by the addition of glycerol, DMSO and 4-PBA. Despite decreased cell growth and viable cell density, production of Alb-EPO was enhanced by chemical chaperones. The highest titer of Alb-EPO was 52.9 mg/L with 1 mM 4-PBA, which is 1.36-fold higher than that of control. The addition of glycerol and DMSO to culture medium also improved production of Alb-EPO titer. Furthermore the relative level of sialylation was enhanced by the addition of glycerol and 4-PBA. Therefore, it is clear that the use of chemical chaperones may be beneficial for the protein quality and production of recombinant proteins.