Enhanced production of recombinant proteins by a small molecule protein synthesis enhancer in combination with an antioxidant in recombinant Chinese hamster ovary cells

Abstract

The improvement in the production of recombinant proteins has been linked in a number of small molecules such as carboxylic acids to the inhibition of histone deacetylase, leading to increased transcription of genes. However, carboxylic acids such as pentanoic acid and butanoic acid have been shown to promote an apoptotic response in Chinese hamster ovary (CHO) cell culture. Supplementation of cultures with antioxidants has shown the ability to reduce the apoptotic response of carboxylic acid supplementation, leading to increased therapeutic protein production. In this study, we showed that pentanoic acid reduced the number of cells entering early apoptosis relative to butanoic acid by 15.4%. Additionally, supplementation of butanoic acid- and pentanoic acid-treated cultures with N-acetyl cysteine (NAC) reduced the population of cells entering early apoptosis by 5.3 and 10.0%, respectively, while increasing productivity by 19.5% in the presence of pentanoic acid and NAC. Conversely, a decrease of 5.7% in production was observed in response to combined butanoic acid and N-acetyl cysteine treatment. The results presented herein provide evidence that a culture supplementation method is critical for optimization of biopharmaceutical manufacturing processes.

Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis

“…However, notice that while other SCFAs, have been used to increase heterologous proteins production ( McMurray-Beaulieu et al, 2009 ; Camire et al, 2017 ) this is not the case of NaAc where the results are more contradictories. In general, much effort has been put to support two possible mechanisms behind the role of SCFA’s in the cell productivity.…”