Developing Next-Generation Inducible Gene Expression Systems for Biopharmaceutical Manufacturing

Biopharmaceuticals offer therapeutic promise for treating many currently incurable conditions, including cancer, neurological disorders and cardiovascular diseases. The manufacture of these therapies is underpinned by production of proteins (e.g. monoclonal antibodies) and viral vectors (e.g. for gene therapies) in mammalian cell factories. These products pose a significant challenge to the cell's machinery and in some cases are toxic, placing significant limitations on the amount of product that can be made in each manufacturing process. This project will develop inducible gene expression systems that can be used to precisely control the timing and level of recombinant protein production, facilitating significant increases in biopharmaceutical product titer and quality. The design space of DNA/RNA features and chemical ligands will be comprehensively mapped and utilised to create next-generation expression systems (i.e. controlling transcription and translation) that are specifically optimised for use in recombinant protein and viral vector production systems. Following multiple rounds of the synthetic biology design-build-test-learn cycle, optimal synthetic genetic parts will be reduced to practice by validating their performance in industrial systems, via collaboration with biopharmaceutical companies.