Development of a CHO production medium utilizing proteomic and metabolomics analysis
May 6-11, 2018
productivity. Metabolomics and proteomic analysis was conducted on two medium formulations with disparate growth and production characteristics. Medium formulation 1 (M1) demonstrates moderate peak VCD with a high specific productivity (qP) over a 14 day growth performance assay utilizing a recombinant IgG producing CHO-S cell line and DG44 cell line. Medium formulation 2 (M2) demonstrates a high peak VCD with moderate qP under the same conditions and cell line. A comparative analysis of metabolite abundance and enzyme regulation identified that M1 had greater flux in the sorbitol pathway verses glycolysis, the TCA cycle was upregulated to a greater degree than M2. A Design of Experiment (DoE) study was developed to increase the specific productivity of M1 without decreasing the VCD to M2 levels resulting in a superior volumetric titer. Simultaneously, we utilized traditional empirical approaches to increase the qP of M2 in a parallel set of experiments. We describe here the path to develop the medium, metabolic and proteomic pathways which were found to be important, and a comparison of results based on the traditional empirical path verses the hypothesis based advanced cellular analytics path.
Paul Gulde, James Smith, Jamie LaPierre, William Paul, Ryan Boniface, Anson Pierce, Paul Gulde, Andrew Campbell, and Nicole DiNardo, "Development of a CHO production medium utilizing proteomic and metabolomics analysis" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/ccexvi/87