Using transcription and translation regulators to improve recombinant protein expression in CHO cells

Chinese hamster ovary (CHO) cells are the predominant platform for the production of recombinant therapeutic proteins (RTPs). Over the past two decades, numerous strategies have focused on increasing the growth, titer and quality of RTPs in CHO cells and concomitantly reducing production costs. Transcription and translation are continuous processes that are crucial for RTP production. Transcription factors (TFs) are predominantly involved in the regulation of growth, metabolism, and endoplasmic reticulum function, and TF engineering has been demonstrated to be an efficacious strategy for enhancing RTP expression, enabling the design of customized TFs and promoters. Translation regulators encompass translation, folding, secretion, and post-translational modifications and involve a multitude of key genes and signaling pathways, which are vital for the immunogenicity of RTPs. Novel synthetic biology methods and advancements in genomics have played significant roles in the design of specific TFs and the selection of translation factors. This review summarizes the strategies for increasing RTP expression in CHO cells via TFs and translation factors. We also propose methods to further optimize protein expression strategies and develop more efficient CHO cell lines by leveraging advancements in genomics and synthetic biology research.