Sugar and Spice:  Systems Biotechnology Approaches to Interpret and Improve Mammalian Cell Factories

Recombinant therapeutics are often complex proteins that require multiple post-translational modifications including glycosylation and protein assembly among other changes. Their biological function and in vivo circulatory activity can depend intimately on these processing events, often occurring within the secretory compartments of the producer cells. Most importantly, a number of factors can impact glycosylation in Chinese hamster ovary and other cell lines. Therefore, the capacity to both elucidate and manipulate these modifications will be useful going forward. In this study, engineering and analytic methods are being applied to both determine the glycosylation structures and if needed change these glycoforms. One approach being used to is to alter the cell lines in order to alter the glycosylation capabilities of CHO cells. Another alternative is to alter the media such that the glycosylation patterns change. It is equally important to be able to analyze the effect of these engineering modifications and thus analytical tools must be implemented to evaluate the glycan patterns on proteins emerging from these hosts. Finally, it is also important to understand the impact of changes to the cell processing capabilities and mathematical modeling tools can be helpful both for understanding how these processing events occur and controlling them for a desired outcome. Such a comprehensive systems approach will enhance our ability to control mammalian glycosylation and other cellular events and in turn lead to improved qualities for target biopharmaceuticals in the future.