Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells

  • Cho, Hee Jun (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Oh, Byung Moo (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Jong-Tae (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lim, Jeewon (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Park, Sang Yoon (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hwang, Yo Sep (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Baek, Kyoung Eun (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Bo-Yeon (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Choi, Inpyo (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Hee Gu (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2018.11.22
  • Accepted : 2018.11.29
  • Published : 2019.02.28
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Abstract

Interleukin-21 is a common ${\gamma}$-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted $IFN-{\gamma}$ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

Keywords

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