Large Scale Bubble Bed Aeration for Animal Cell Cultures

Trocha, M.; Rohr, Rudolf von

doi:10.1007/978-94-011-5404-8_63

Cited by 1 publication

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“…To maintain the high productivity, oxygen has to be supplied continuously but rigorous agitation for oxygenation causes cell death. Although a variety of physical methods for aeration with reduced detrimental effect on animal cells have been developed, a method of oxygen supply for higher productivity, particularly in a large scale culture with high cell densities, remains to be devised (Kelly et al, 1993;Trocha et al, 1997;Born et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

A new biological strategy for high productivity of recombinant proteins in animal cells by the use of hypoxia-response enhancer

Masuda

Moon

Kambe

et al. 2000

Biotechnol. Bioeng.

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Oxygen supply is one of the major problems in the production of useful proteins by cultured animal cells and therefore it is of importance to devise a system by which a high productivity of human therapeutic recombinant proteins can be maintained or enhanced under low oxygen concentrations. A number of hypoxia‐inducible genes have been found in animal cells and the induction in most cases is due to hypoxic activation of the gene transcription. A consensus sequence (HRE = hypoxia‐response enhancer) responsible for the hypoxic activation exists in these genes and the binding of a protein, which is widely distributed in animal cells, to this sequence responding to hypoxia activates the promoter activity. The promoter of lactate dehydrogenase A gene is active in Chinese hamster ovary (CHO) cells and the vicinal HRE stimulates the promoter activity efficiently in hypoxia. We have prepared a number of permanent CHO cell lines producing recombinant human erythropoietin (Epo) under control of this promoter/HRE. Epo production was highly hypoxia‐inducible when the wild‐type of HRE was used but uninducible when the mutant HRE was used. There was little difference in the in vitro and in vivo activities, and glycosylation between Epo produced by the cells cultured in 21% and 2% oxygen. Furthermore, forced expression of hypoxia‐inducible factor‐1α (HIF‐1α) enhanced Epo production in all oxygen concentrations. These results indicate that a biological strategy based on the hypoxic induction of gene transcription provides a novel system which guarantees a high productivity even uner low oxygen concentrations. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 67: 157–164, 2000.

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Section: Introductionmentioning

confidence: 99%