High productivity of t-PA in CHO cells using hypoxia response element

Gun Won Bae, Dae Won Jeong, Hong Jin Kim, Gyun Min Lee, Hongwoo Park, Tae Boo Choe, Seongman Kang, Ick Young Kim, Ik Hwan Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The dissolved oxygen level of any cell culture environment has a critical effect on cellular metabolism. Specifically, hypoxia condition decreases cell viability and recombinant protein productivity. In this work, to develop CHO cells producing recombinant protein with high productivity, mammalian expression vectors containing a human tissue-type plasminogen activator (t-PA) gene with hypoxia response element (HRE) were constructed and stably transfected into CHO cells. CHO/2HRE-t-PA cells produced 2-folds higher recombinant t-PA production than CHO/t-PA cells in a Ba2+-alginate immobilized culture, and 16.8-folds in a repeated batch culture. In a non-aerated batch culture of suspension-adapted cells, t-PA productivity of CHO/2HRE/t-PA cells was 4.2-folds higher than that of CHO/t-PA cells. Our results indicate that HRE is a useful tool for the enhancement of protein productivity in mammalian cell cultures.

Original languageEnglish
Pages (from-to)695-703
Number of pages9
JournalJournal of microbiology and biotechnology
Volume16
Issue number5
Publication statusPublished - 2006 May

Keywords

  • Chinese hamster ovary cell
  • Hypoxia
  • Hypoxia inducible factor-1α
  • Hypoxia response element
  • Immobilized cells
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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  • Cite this

    Bae, G. W., Jeong, D. W., Kim, H. J., Lee, G. M., Park, H., Choe, T. B., Kang, S., Kim, I. Y., & Kim, I. H. (2006). High productivity of t-PA in CHO cells using hypoxia response element. Journal of microbiology and biotechnology, 16(5), 695-703.