Genome engineering and synthetic biology approaches for improving industrial CHO cell production of biologics

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Biologics are protein-based biopharmaceutical drugs that are used in a variety of diseases. The overall market for biopharmaceuticals is steadily increasing and in 2013 generated sales in excess of $140 billion. The Lonza GS platform is considered industry leading with 18 marketed products, and over 100 in active human trials. Despite this success, there are increasing numbers of "difficult-to-express" biologics reaching the pipeline. The new technologies of rational genome and gene circuit engineering promise new ways of regulating biologic expression to maximise production, while reducing toxicity. The aim is to build "genetic thermostats" to prevent toxic proteins from shutting down cellular production altogether, using genetic feedback. The final goal of this feasibility study is to pave the way for the development of a robust and one-fits-all cell line platform for the production of "difficult-to-express" biologics.