Development of a CHO production medium utilizing proteomic and metabolomics analysis

Conference Dates

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.

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