Researchers from the U.K. are working to boost protein secretion in a common biomanufacturing cell type by changing how the proteins are regulated. Mauro Torres, PhD, a research associate from the Manchester Institute of Biotechnology, is modifying regulatory transcription factors to help increase the amount of protein product produced in a bioreactor by Chinese Hamster Ovary (CHO) cells.

According to Torres, “During the last twenty or thirty years, there’s been a major improvement in how you can modify the [cell] culture, such as […] the nutrients, [and increase] the gene copy number within the cells, but one thing that’s lacking is how the cellular machinery can handle these improvements.”

Many improvements in manufacturing, such as how the nutrient mix in the bioreactor, can be stressful for CHO cells, Torres explains. The inspiration for his research was how to make the cells more resilient by using genetic engineering.

Torres is using transcription factors to activate or suppress certain genes, including those that can increase protein production. He explains that he designs a vector that can be introduced into cells to see whether they overexpress a protein.

“CHO cells are permissive to the insertion of vectors,” he says, and the team used electroporation or chemicals to diffuse the recombinant gene through the cell membrane. The researchers hope that, in the future, CHO cells may be engineered using synthetic biology to meet a specific purpose, such as with features useful for continuous processing.

As Torres explains, synthetic biology can be used to create a new expression system regulated by, for example, doxycycline. This means that the amount of gene expression can be switched on and off, or precisely controlled.

“You can design cells with all features controllable,” he says. “And can ask the question: how do you design cells with the end [use/product] in mind?”

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