Gene

Context (archaeology)

Cell biology

Biopharmaceutical

Biotechnology

Biology

Reactive oxygen species

Cell culture

Chinese hamster ovary cell

Receptor

Biochemistry

Botany

Paleontology

Intracellular

Genetics

Oxidative phosphorylation

Oxidative stress

Antioxidant

Chemistry

Bioreactor

Recombinant DNA

Biotechnology and Bioengineering

Large scale biopharmaceutical production of biologics relies on the overexpression of foreign proteins by cells cultivated in stirred tank bioreactors. It is well recognized and documented fact that protein overexpression may impact host cell metabolism and that factors associated with large scale culture, such as the hydrodynamic forces and inhomogeneities within the bioreactors, may promote cellular stress. The metabolic adaptations required to support the high‐level expression of recombinant proteins include increased energy production and improved secretory capacity, which, in turn, can lead to a rise of reactive oxygen species (ROS) generated through the respiration metabolism and the interaction with media components. Oxidative stress is defined as the imbalance between the production of free radicals and the antioxidant response within the cells. Accumulation of intracellular ROS can interfere with the cellular activities and exert cytotoxic effects via the alternation of cellular components. In this context, strategies aiming to alleviate oxidative stress generated during the culture have been developed to improve cell growth, productivity, and reduce product microheterogeneity. In this review, we present a summary of the different approaches used to decrease the oxidative stress in Chinese hamster ovary cells and highlight media development and cell engineering as the main pathways through which ROS levels may be kept under control.

Oxidative stress‐alleviating strategies to improve recombinant protein production in CHO cells