Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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High Productivity of t-PA in CHO Cells Using Hypoxia Response Element

  • Bae Gun-Won (College of Life Sciences and Biotechnology, Korea University) ;
  • Jeong Dae-Won (BK21 HLS, Seoul National University) ;
  • Kim Hong-Jin (Microbiology Section, College of Pharmacy, Chung Ang University) ;
  • Lee Gyun-Min (Department of Biological Sciences, KAIST) ;
  • Park Hong-Woo (Division of Applied Chemical Engineering & Bio Engineering) ;
  • Choe Tae-Boo (Department of Microbiological Engineering) ;
  • Kang Seong-Man (College of Life Sciences and Biotechnology, Korea University) ;
  • Kim Ick-Young (College of Life Sciences and Biotechnology, Korea University) ;
  • Kim Ik-Hwan (College of Life Sciences and Biotechnology, Korea University)
  • Published : 2006.05.01
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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 $Ba^{2+}-alginate$ 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.

Keywords

References

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