The traditional engineering paradigm states that you must sacrifice quality for quantity.  This can be true for biomanufacturing processes in which quality can involve critical quality attributes such as the glycan structures attached to a produced glycoprotein therapeutic.  As biotechnologists, we seek to break this axiom through the application of systems engineering, cell and process modeling, and synthetic biology and metabolic engineering.  In our current work we are implementing these systems biotechnology tools to improve the performance of CHO cells and other production hosts.   Engineering methodologies are being applied to both determine the glycosylation structures and, as needed, change these glycoforms.  One approach being used is to alter the cell lines in order to both add and remove glycosylation capabilities in CHO cells.  Determining which modifications are best to implement can be facilitated with the assistance of comprehensive models of glycosylation processes.   Another alternative is to adjust the media and examine the role that changes to its composition including supplementation with additives has on both the product titer and glycosylation character.  It is equally important to be able to evaluate the effect of these engineering modifications and thus analytical tools are used to determine the glycan patterns for glycoproteins produced in  these hosts.  Finally, it is also useful to dictate the final glycan structures and this is often best achieved through the use of control strategies based on our understanding of cellular glycosylation and the impact of process modifications.  Such a comprehensive systems biotechnology approach will enhance our ability to generate desired profiles in terms of glycosylation and other quality attributes while minimizing the effect on the performance of CHO cells in culture, leading to enhanced qualities and yields for target biopharmaceuticals in current and future mammalian biomanufacturing processes.

Gaden award: Quality and quantity? Enhancing mammalian biomanufacturing performance through systems biotechnology approaches

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.