Autophagy and its implication in Chinese hamster ovary cell culture

Abstract

Chinese hamster ovary (CHO) cells, that are widely used for production of therapeutic proteins, are subjected to apoptosis and autophagy under the stresses induced by conditions such as nutrient deprivation, hyperosmolality and addition of sodium butyrate. To achieve a cost-effective level of production, it is important to extend the culture longevity. Until now, there have been numerous studies in which apoptosis of recombinant CHO (rCHO) cells was inhibited, resulting in enhanced production of therapeutic proteins. Recently, autophagy in rCHO cells has drawn attention because it can be genetically and chemically controlled to increase cell survival and productivity. Autophagy is a global catabolic process which involves multiple pathways and genes that regulate the lysosomal degradation of intracellular components. A simultaneous targeting of anti-apoptosis and pro-autophagy could lead to more efficient protection of cells from stressful culture conditions. In this regard, it is worthwhile to have a detailed understanding of the autophagic pathway, in order to select appropriate genes and chemical targets to manage autophagy in rCHO cells, and thus to enhance the production of therapeutic proteins.