Analysis of foreign protein overproduction in recombinant CHO cells. Effect of growth kinetics and cell cycle traverse.

Abstract:

: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.

journal_name

Ann N Y Acad Sci

authors

Gu MB,Todd P,Kompala DS

doi

10.1111/j.1749-6632.1994.tb47392.x

subject

Has Abstract

pub_date

1994-05-02 00:00:00

pages

194-207

eissn

0077-8923

issn

1749-6632

journal_volume

721

pub_type

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