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Use of a structured kinetic model of antibody synthesis and secretion for optimization of antibody production systems: I. Steady‐state analysis
Author(s) -
Bibila Theodora A.,
Flickinger Michael C.
Publication year - 1992
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.260390302
Subject(s) - secretion , antibody , steady state (chemistry) , immunoglobulin light chain , intracellular , chemistry , biology , biochemistry , immunology
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.