The role of the cell cycle in determining gene expression and productivityin CHO cells

Understanding the relationships between cell cycle and protein expression i s critical to the optimisation of media and environmental conditions for su ccessful commercial operation of animal cell culture processes. Using flow cytometry for the analysis of the early phases of synchronised batch cultur es, the dependency of product expression on cell cycle related events has b een evaluated in a recombinant CHO cell line. Although the production of re combinant protein is initially found to be cell cycle related, the maximum specific protein productivity is only achieved at a later stage of the expo nential phase which also sees a maximum in the intracellular protein concen tration. Subsequent work suggests that it is the batch phase/medium composi tion of cultures which is the major determinant of maximum specific product ivity in this cell line. Furthermore the effect of the positive association between S phase and specific productivity is subordinate to the effect of batch phase/medium composition on the specific productivity of batch cultur es.