Hypoxia-Induced Production of Recombinant Erythropoietin Using Hypoxia-Response Enhancer

Abstract

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. To overcome the reduced productivity of recombinant protein in a low oxygen concentration, we have developed a new recombinant protein production system using hypoxia-response enhancer. We have prepared a permanent CHO cell lines producing recombinant human Epo under control of LDHA promoter/HRE. Epo production was highly hypoxia inducible. 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. 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 under low oxygen concentrations.