Scientists crack the code to boost therapeutic protein production in cells
A groundbreaking study, led by Dr. Nathan Lewis and Dr. Johan Rockberg, explores the complexities of protein production in Chinese hamster ovary (CHO) cells. The research, published in the Proceedings of the National Academy of Sciences, illuminates why certain therapeutic proteins are challenging to manufacture using these cells, with substantial implications for the biopharmaceutical industry.
The study revealed that the most significant differences in protein production weren't due to the abundance of transgene mRNA, but rather the cells' own gene-expression programs. Poorly performing cells activated stress pathways, while high-performing cells bolstered lipid metabolism and oxidative stress resistance. This understanding could transform the biopharmaceutical industry, which relies on CHO cells to produce billions of dollars' worth of lifesaving drugs.
The study scrutinized the expression of over 1,000 human secreted proteins in CHO cells. It was discovered that longer proteins tend to express poorly due to increased chances of misfolding. However, protein physicochemical features like size and cysteine content explained about 15% of the variability in protein yield. The study also pinpointed specific amino-acid compositions and post-translational modifications that forecast expression success, offering precious guidance for protein design and cell-line engineering.
Subsequent research aims to comprehend and manipulate metabolic 'switches' in CHO cells, particularly those involving lipid metabolism, to amplify protein production. This could result in more efficient and cost-effective production of therapeutic proteins.
The study, published in the Proceedings of the National Academy of Sciences, offers a comprehensive understanding of protein production in CHO cells. By identifying the key factors influencing protein yield, the research clears the path for enhanced protein design and cell-line engineering. This could substantially impact the biopharmaceutical industry, leading to more efficient and cost-effective production of lifesaving drugs.
