Zhang Huan-Yu, Fan Zhen-Lin, Wang Chong, Li Jia-Yue, Feng Hui-Gen, Wang Xiao-Yin, Wang Tian-Yun
Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453000, China; Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang 453000, China.
International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang 453000, China.
Int J Biol Macromol. 2025 May;309(Pt 2):142822. doi: 10.1016/j.ijbiomac.2025.142822. Epub 2025 Apr 3.
Chinese hamster ovary (CHO) cells are major expression platforms for the transient production of recombinant therapeutic proteins (RTPs). Most improvement strategies have focused on promoting transcriptional expression in CHO cells. However, methods for promoting the yield of RTPs through translational regulation remain unclear. In this study, we investigated characteristics of the 5'-untranslated region (UTR) that influence recombinant protein expression in CHO cells and identified sequences that have positive effects on protein expression using ribosome sequencing. Some elements and characteristics of 5'-UTR differentially affected the translation of the main open reading frame and increased recombinant protein expression by 1.5-fold in CHO cells. The findings may help relieve the bottleneck of the yield of RTPs on translation enhancement.
中国仓鼠卵巢(CHO)细胞是重组治疗性蛋白(RTP)瞬时生产的主要表达平台。大多数改进策略都集中在促进CHO细胞中的转录表达上。然而,通过翻译调控提高RTP产量的方法仍不明确。在本研究中,我们研究了影响CHO细胞中重组蛋白表达的5'非翻译区(UTR)的特征,并通过核糖体测序鉴定了对蛋白表达有积极影响的序列。5'-UTR的一些元件和特征对主要开放阅读框的翻译有不同影响,并使CHO细胞中的重组蛋白表达增加了1.5倍。这些发现可能有助于缓解RTP产量在翻译增强方面的瓶颈。