期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 118, 期 5, 页码 1876-1883出版社
WILEY
DOI: 10.1002/bit.27703
关键词
autophagy; batch; CHO; fed‐ batch; recombinant protein production
资金
- Natural Sciences and Engineering Research Council of Canada
- University of British Columbia
- Saskatchewan Health Research Foundation
The modulation of autophagy has shown to increase productivity in CHO cell cultures, with the addition of AIP leading to a concentration-dependent enhancement in protein yield. However, this also results in a temporary drop in cell viability.
The development of generic biopharmaceuticals is increasing the pressures for enhanced bioprocess productivity and yields. Autophagy (self-eating) is a cellular process that allows cells to mitigate stresses such as nutrient deprivation. Reputed autophagy inhibitors have also been shown to increase autophagic flux under certain conditions, and enhance recombinant protein productivity in Chinese Hamster Ovary (CHO) cultures. Since peptides are commonly added to bioprocess culture media in hydrolysates, we evaluated the impact on productivity of an autophagy-inducing peptide (AIP), derived from the cellular autophagy protein Beclin 1. This was analyzed in CHO cell batch and fed-batch serum-free cultures producing a human Immunoglobulin G1 (IgG1). Interestingly, the addition of 1-4 mu M AIP enhanced productivity in a concentration-dependent manner. Cell-specific productivity increased up to 1.8-fold in batch cultures, while in fed-batch cultures a maximum twofold increase in IgG concentration was observed. An initial drop in cell viability also occurred before cultures recovered normal growth. Overall, these findings strongly support the value of investigating the effects of autophagy pathway modulation, and in particular, the use of this AIP medium additive to increase CHO cell biotherapeutic protein production and yields.
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