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Analysis of Foreign Protein Overproduction in Recombinant CHO Cells
Author(s) -
GU MAN BOCK,
TODD PAUL,
KOMPALA DHINAKAR S.
Publication year - 1994
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1994.tb47392.x
Subject(s) - overproduction , recombinant dna , chemistry , chinese hamster ovary cell , microbiology and biotechnology , biology , biochemistry , gene , receptor
Intracellular foreign protein (beta-galactosidase) expression in recombinant CHO cell lines in continuous culture was analyzed by developing a mathematical model that includes the effects of metabolic burden and cell cycle dependence of intracellular foreign protein expression. This combined growth kinetic and cell cycle model, assuming S- or G1-phase-dependent expression, was stimulated to predict productivity on a single-cell and culture-volume basis in continuous cultures. In the case of S-phase-dependent expression, the intracellular foreign protein level increases monotonically, but in the case of G1-phase-dependent expression it decreases monotonically with increasing dilution rate. Also, the trends of foreign protein concentration in the culture volume differ significantly between S- and G1-dependent expression kinetics. Thus, the cell cycle dependency of foreign protein expression should be included in process optimization concepts and operating strategies of continuous bioreactors.