Using endoplasmic reticulum engineering to improve recombinant protein production in CHO cells.

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.