Performance Period: 3/1/2019 to 2/28/2021
Glucose metabolism plays a central role in cell physiology. Cells in culture have a high flux of glucose consumption and convert a large portion of the consumed glucose to lactate. In the late stage of fed-batch culture, the high flux metabolism may switch to low flux. The occurrence, or the lack thereof, of metabolic shift in fed-batch cultures affects the productivity and quality of therapeutic proteins. However, the behavior of such a metabolic shift varies among different production cell lines, and in some cases, even among manufacturing runs using the same production cell line.
This project will develop a mechanistic model of cell metabolism that can be integrated with a multiscale cell growth model to predict of metabolic behavior in fed-batch culture. The metabolic profile of three cell lines will be characterized to determine the kinetic parameters and cell specific model will be established for the three cell lines. The model will allow for a rational design of fed-batch processes to increase process robustness. The technology is currently at MRL3 and will be at level 4 upon the completion of the project.
Availability of a mechanistic model for cell metabolism integrated with a multiscale cell growth model to predict of metabolic behavior in fed-batch culture including productivity and quality of therapeutic proteins.
O’Brien, C. M., Zhang, Q., Daoutidis, P., & Hu, W. (2021). A hybrid mechanistic-empirical model for in silico mammalian cell bioprocess simulation. Metabolic Engineering, 66, 31–40. https://doi.org/10.1016/j.ymben.2021.03.016
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Regents of University of Minnesota
Merck Sharp & Dohme LLC
Metalytics
MilliporeSigma/EMD Serono
