自噬
生物过程
水解物
化学
生物
中国仓鼠卵巢细胞
细胞生物学
生产力
补料分批培养
重组DNA
单克隆抗体
细胞培养
生物化学
抗体
发酵
免疫学
基因
遗传学
宏观经济学
古生物学
经济
水解
细胞凋亡
作者
Katrin Braasch,Marko Kryworuchko,James M. Piret
出处
期刊:Authorea - Authorea
日期:2020-09-14
标识
DOI:10.22541/au.160010778.80458067
摘要
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 IgG1. Interestingly, the addition of 1 to 4 µM 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 2-fold increase in volumetric productivity 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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