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

Man Bock Gu, P. Todd, D. S. Kompala

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Intracellular foreign protein (β-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 simulated 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.

Original languageEnglish
Pages (from-to)194-207
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume721
DOIs
Publication statusPublished - 1994 Jul 15
Externally publishedYes

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CHO Cells
Growth kinetics
Cell Cycle
Cells
Growth
G1 Phase
Proteins
Galactosidases
Bioreactors
S Phase
Cell Size
Dilution
Theoretical Models
Cell Culture Techniques
Productivity
Kinetics
Protein
Mathematical models
Cell Line

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Analysis of foreign protein overproduction in recombinant CHO cells. Effect of growth kinetics and cell cycle traverse. / Gu, Man Bock; Todd, P.; Kompala, D. S.

In: Annals of the New York Academy of Sciences, Vol. 721, 15.07.1994, p. 194-207.

Research output: Contribution to journalArticle

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