Advances in cell cycle regulation to enhance recombinant protein production in CHO cells

Chinese hamster ovary (CHO) cells have become the predominant host system in biopharmaceutical production due to their unique capacity to generate recombinant proteins with complex structures and human-like post-translational modifications. However, low expression levels and product heterogeneity remain critical bottlenecks requiring urgent resolution in CHO cell applications. Current strategies encompass culture condition optimization, vector design improvements, and cell engineering approaches targeting expression regulation mechanisms. Among these approaches, cell cycle regulation has garnered significant attention due to its intrinsic connection to transcriptional activity and biosynthetic processes. Each phase of the cell cycle is tightly regulated and exerts phase-specific influences on gene expression patterns, including temporal control of transcriptional activity, functional specialization, and modulation of cellular processes. Consequently, cell cycle engineering strategies targeting key regulatory nodes - such as cyclin-dependent kinases (CDKs), cyclin family proteins, and E2F transcription factors - have emerged as promising approaches to control cell cycle progression/arrest and thereby enhance recombinant protein yields. This review systematically examines the distinct phases and characteristic features of the cell cycle, while comprehensively analyzing the impact of cell cycle regulation on recombinant protein yield in CHO cells and recent research advancements in this field.