Engineering CHO Cells to Achieve a High-Level Inverse-Growth-Associated Production of Secreted Glycoproteins in High Cell Density Cultures

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The objective of this project is to increase the efficiency of cell culture systems by; (a) genetic manipulation of the cells; and (b) utilization of a cell retention system. Genetic manipulation utilizing an AML promoter specific to the G1-phase adds to the benefits of increasing the specific production rate at lower growth rates. Under these conditions, cells can be cultured at low media exchange rates and a higher titer can be achieved. Utilization of a cell retention system increases the cell density and allows a higher volumetric productivity. The CHO expression system considered in this proposal is extensively used in industry and the results from this research will be very applicable to industrial manufacturing.