CHO 세포 배양에서 미토콘드리아 생합성 유도를 통한 재조합 단백질 생산성 증대

초록

Mitochondria are the powerhouse of a cell that produces cellular energy, especially adenosine triphosphate (ATP), to fuel cell biosynthesis and protein production. In this study, we aim at inducing mitochondrial biogenesis in Chinese hamster ovary (CHO) cells to increase cellular ATP levels as well as recombinant protein productivity. Focusing on the culture process engineering, we tested two chemical additives, resveratrol and nicotinamide adenine dinucleotide (NAD), in CHO cell cultures to reinforce mitochondrial biogenesis. Resveratrol and NAD treatment resulted in an increase in specific productivity (q p ) by 10-30% and 40-50% compared to the control, respectively. In addition, NAD exhibited an increase in viable cell densities, culture longevity and specific lactate uptake rates. Moreover, along with an increase in the ATP level, mitochondrial DNA (mtDNA) copy number and mRNA expression of the mitochondrial biogenesis-related genes were also up-regulated compared to the control. In conclusion, although there might be varied cell line-specific impacts on cell growth, inducing mitochondrial biogenesis using chemical additives would be an effective strategy for improving recombinant proteins productivity in CHO cells culture.

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