The secretory pathway - the key for unlocking the potential of Chinese hamster ovary cell factories for manufacturing therapeutic proteins

Mammalian cell factories (in particular the CHO cell system) have been crucial in the rise of biopharmaceuticals. Mammalian cells have compartmentalized organelles where intricate networks of proteins manufacture highly sophisticated biopharmaceuticals in a specialized production pipeline - the secretory pathway. In the bioproduction context, the secretory pathway functioning is key for the effectiveness of cell factories to manufacture these life-changing medicines. This review describes the molecular components and events involved in the secretory pathway, and provides a comprehensive summary of the intracellular steps limiting the production of therapeutic proteins as well as the achievements in engineering CHO cell secretory machinery. We also consider antibody-producing plasma cells (so called professional secretory cells) to explore the mechanisms underpinning their unique secretory function/features. Such understandings offer the potential to further enhancement of the current CHO cell production platforms for manufacturing next generation of biopharmaceuticals.

Automated summary

This review highlights the importance of mammalian cell factories, particularly the CHO cell system, in biopharmaceutical production. It provides an overview of the secretory pathway, the challenges in protein production, and the advancements in engineering CHO cell secretory machinery. The understanding of the mechanisms underlying the unique secretory function of antibody-producing plasma cells offers potential for further improvement in biopharmaceutical manufacturing.