USE OF A STRUCTURED KINETIC-MODEL OF ANTIBODY-SYNTHESIS AND SECRETION FOR OPTIMIZATION OF ANTIBODY-PRODUCTION SYSTEMS .1. STEADY-STATE ANALYSIS

被引:37
|
作者
BIBILA, TA
FLICKINGER, MC
机构
[1] UNIV MINNESOTA, DEPT BIOCHEM, ST PAUL, MN 55108 USA
[2] UNIV MINNESOTA, DEPT CHEM ENGN & MAT SCI, ST PAUL, MN 55108 USA
[3] UNIV MINNESOTA, INST ADV STUDIES BIOL PROC TECHNOL, ST PAUL, MN 55108 USA
关键词
MONOCLONAL ANTIBODY SECRETORY PATHWAY; STRUCTURED KINETIC MODEL; FACTORIAL DESIGN; STEADY-STATE SIMULATIONS;
D O I
10.1002/bit.260390302
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 light-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.
引用
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页码:251 / 261
页数:11
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