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Chinese hamster ovary (CHO) cell lines have been widely used to produce recombinant proteins. While the biosynthesis of recombinant proteins is energy-intensive, CHO cells exhibit inefficient metabolism, characterized by rapid conversion of glucose to lactate, possibly leading to lower cell growth and productivity of therapeutic proteins. Therefore, it is important to understand and engineer cellular metabolism to increase recombinant protein production. In this review, cellular energy metabolism of CHO cells with respect to protein synthesis is overviewed. Then, genetic and process engineering approaches to enhance metabolic efficiency are described, resulting in the improvement of cell culture performance. Finally, recent modeling technologies for understanding and predicting cellular metabolic behaviors are reviewed. These efforts will aid to further advance the biomanufacturing of therapeutic proteins. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary (CHO) cell cultures are widely used due to their high productivity, industrial track record, safety record, and correct post-translational modifications. Fed-batch and perfusion modes have been mostly adopted as traditional commercial manufacturing process using CHO cells for the production of biopharmaceuticals. Thus, we compared fed-batch and perfusion culture processes for the commercial-scale production of monoclonal antibody. Main production process was performed after confirming the comparable culture performance in seed train of different operation modes, and then perfusion cultures showed 1.6-fold higher peak viable cell density (VCD) with a longer culture duration than that of fed-batch cultures. Also, as the result of main batches, total product amount increased over 450% in perfusion cultures. Importantly, perfusion process allowed to improve the higher purification yield while maintaining acceptable product quality, because the level of process impurity could be reduced by using retention device. When economic comparison of fed-batch versus perfusion processes was carried out under the equal scale of upstream and downstream, perfusion mode was more a cost-effective bioprocess that could reduce the cost of goods. In conclusion, although comparison data of triplicate commercial batches are of course specific case for a given antibody production, this study verified the possibility of using perfusion mode as an efficient system for commercial producing the desired antibody and is a meaningful report in the biopharmaceutical industry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of suramin in CHO cell cultures in terms of the cell culture performance and quality of the Fc-fusion protein. Results: Suramin had positive effects on the CHO cell cultures. The addition of suramin caused an increase in the viable cell density, cell viability, and titer of the Fc-fusion protein. Moreover, suramin had no impact on protein aggregation and enhanced the sialic acid contents of Fc-fusion protein by 1.18-fold. The enhanced sialylation was not caused by the increased nucleotide sugar level but by the inhibition of sialidase activity. The results showed that suramin inhibited apoptosis and had positive impacts on the productivity and quality of Fc-fusion protein. Conclusion: The addition of suramin increased the production of Fc-fusion protein and enhanced sialylation when added as a supplement to the media component in CHO cell cultures. This study suggested that suramin could be a beneficial additive during the biological production in terms of the productivity and quality of Fc-fusion protein. [ABSTRACT FROM AUTHOR]