Use of a structured kinetic model of antibody synthesis and secretion for optimization of antibody production systems: I. Steady-state analysis.
Steady-state simulations using our previously developed structured kinetic model of antibody synthesis and secretion by hybridoma cells are used here in conjunction with factorial design analysis to identify intracellular parameters important in determining the specific antibody secretion rate and predict the dependence of this rate on cell specific growth rate. Simulation results suggest that the specific growth rate, the assembly rate of the heavy and light chains and the heavy- and -chain gene dosage can significantly affect the rate of antibody secretion. Based on these results, environmental and/or genetic manipulation approaches are proposed for maximizing the specific antibody secretion rate and the antibody volumetric productivity in large-scale antibody production systems.
Bibila
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Department of Chemical Engineering and Materials Science and Institute for Advanced Studies, in Biological Process Technology, University of Minnesota, St. Paul, Minnesota 55108, USA.
Flickinger
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