Exploring the effect of mild hypothermia on CHO cell productivity

The CHO cell line is mainly used to synthesize recombinant proteins for human therapeutic use. Recent efforts have focused on improving the productivity of this system by mainly using two tools: genetic manipulation of the cells and/or changing the operating conditions of the cultures. In most cases, these techniques have resulted in significant improvements to the productivity of the system. For example, a slight decrease in culture temperature has been used over the past ten years to increase culture longevity, resulting in an increased productivity of r-proteins. However, despite large numbers of diverse studies, there are currently no unified hypotheses to explain the increased productivity of r-proteins. This is mainly because the magnitude of this effect is dependent on the cell line and the r-protein, and the effects of temperature on cellular processes of protein synthesis and cell growth are difficult to decouple and quantify experimentally. In this review, we assembled the most relevant backgrounds to address this problem, and we explore a different experimental approach that allowed us to decouple specific cell growth from culture temperature, in order to estimate the net effect of temperature on the productivity of r-proteins and to better understand the molecular and cellular processes involved. The information provided in this study can be used to propose new strategies at an industrial scale for implementing fed-batch or perfusion cultures to improve the production of several important r-proteins.