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KMID : 0545120190290020304
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Journal of Microbiology and Biotechnology
2019 Volume.29 No. 2 p.304 ~ p.310
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Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells
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Cho Hee-Jun
Oh Byung-Moo
Kim Jong-Tae
Lim Jee-Won
Park Sang-Yoon
Hwang Yo-Sep
Baek Kyoung-Eun
Kim Bo-Yeon
Choi In-Pyo
Lee Hee-Gu
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Abstract
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Interleukin-21 is a common γ-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-γ 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.
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KEYWORD
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IL-21, codon optimization, signal peptide, NK cells, CHO cells
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