Zhang Junhe, Wang Weifeng, Zhang Xi, Wang Fang, Geng Shaolei, Wang Xiaoyin, Wang Tianyun
Institutes of Health Central Plains, Xinxiang Key Laboratory for Tumor Drug Screening and Targeted Therapy, Xinxiang Medical University, Xinxiang 453003, China; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang 453003, China.
Institutes of Health Central Plains, Xinxiang Key Laboratory for Tumor Drug Screening and Targeted Therapy, Xinxiang Medical University, Xinxiang 453003, China; International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang 453003, China.
Int J Biol Macromol. 2025 Jun;315(Pt 2):144695. doi: 10.1016/j.ijbiomac.2025.144695. Epub 2025 May 26.
Chinese hamster ovary (CHO) cells are commonly used to produce recombinant therapeutic proteins (RTPs). While recent strategies have significantly improved the expression levels of RTPs in CHO cells, insufficient secretion and endoplasmic reticulum (ER) stress remain major bottlenecks. Therefore, further understanding of the mechanism of the ER stress response, optimization of ER-related folding and degradation pathways, and development of more efficient ER engineering tools are expected to overcome this issue and maximize RTP production. In this review, we summarize the role of ER in recombinant proteins production and explore ER engineering strategies to improve the yield of recombinant proteins in CHO cells. We further discuss ER-related strategies that can improve recombinant protein production, future research directions, and prospective applications.
中国仓鼠卵巢(CHO)细胞常用于生产重组治疗性蛋白(RTP)。尽管最近的策略显著提高了RTP在CHO细胞中的表达水平,但分泌不足和内质网(ER)应激仍然是主要瓶颈。因此,进一步了解ER应激反应机制、优化ER相关的折叠和降解途径以及开发更有效的ER工程工具有望克服这一问题并最大化RTP的产量。在本综述中,我们总结了ER在重组蛋白生产中的作用,并探索了提高CHO细胞中重组蛋白产量的ER工程策略。我们还进一步讨论了可提高重组蛋白产量的ER相关策略、未来研究方向以及潜在应用。