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Review
. 2025 Jun;315(Pt 2):144695.
doi: 10.1016/j.ijbiomac.2025.144695. Epub 2025 May 26.

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

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Review

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

Junhe Zhang et al. Int J Biol Macromol. 2025 Jun.

Abstract

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.

Keywords: Chinese hamster ovary cells; Endoplasmic reticulum engineering; Endoplasmic reticulum stress; Recombinant protein.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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