2019 ; Vol.29-2: 304~310
|Author||Hee Jun Cho, Byung Moo Oh, Jong-Tae Kim, Jeewon Lim, Sang Yoon Park, Yo Sep Hwang, Kyoung Eun Baek, Bo-Yeon Kim, Inpyo Choi, Hee Gu Lee|
|Place of duty||Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Republic of Korea|
|Title||Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells|
J. Microbiol. Biotechnol.2019 ;
|Abstract||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.|
|Key_word||IL-21, codon optimization, signal peptide, NK cells, CHO cells|
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