The secretory pathway – the key for unlocking the potential of Chinese hamster ovary cell factories for manufacturing therapeutic proteins
Mauro Torres, Hirra Hussain, Alan J. Dickson
Abstract
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.