(194c) Comprehensive Proteomic Analysis of High Productivity CHO Cells

Chinese hamster ovary (CHO) cells have been widely used as host cells for the production of recombinant therapeutic protein. However, the limited understanding of the regulation mechanism of exogenous gene expression in CHO cells has hampered the further improvements of protein production. In this study, a comprehensive proteomics approach was taken to better understand intracellular regulation of recombinant protein expression in CHO cells. Specifically, the global proteomic maps of a high antibody producing cell line (CHO DG44/IgG, volumetric titer >1g/L in shaker flasks) and its host (CHO DG44) were analyzed and compared. The intracellular proteins associated with transcription, translation, post translation modification, as well as carbon and energy metabolism were investigated, and the potential regulators were identified. In addition, proteomic analysis of the antibody producing CHO cells cultivated in batch process and different fed-batch processes were carried out, which was integrated with glucose, glutamine, and amino acid metabolism. This proteomic study can improve comprehension of cellular mechanisms in CHO cells and direct future cell engineering and process optimization.