A study published in the Proceedings of the National Academy of Sciences has unveiled critical insights into the challenges of producing therapeutic proteins in Chinese hamster ovary (CHO) cells. Led by Nathan Lewis, PhD, and Johan Rockberg, PhD, the research analyzes the variability in protein production capabilities of CHO cells, which are the industry standard for biologics.
Despite their widespread use, many human proteins yield low production rates, posing significant hurdles for drug developers. The research team examined over 1,000 human secreted proteins, discovering that less than one percent of yield variability could be attributed to transgene mRNA abundance. Instead, they found that the physicochemical properties of proteins and the host cells’ gene-expression profiles played a more substantial role.
Notably, cells that struggled with protein production activated stress pathways, while high-performing cells enhanced lipid metabolism and resisted oxidative stress. This indicates that successful protein expression is not solely dependent on the recombinant gene but also on the cellular environment. The findings provide a roadmap for pharmaceutical professionals, suggesting that optimizing host cell characteristics could significantly improve protein yield.
Future research will focus on fine-tuning metabolic pathways in CHO cells to enhance production efficiency, potentially transforming the landscape of biologic drug manufacturing.
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