Synthetic biology based polymerase and promoter engineering for production of next-generation mRNA therapeutics

The therapeutic promise of mRNA-based biopharmaceuticals was realised when they formed the backbone of the world's vaccination programme against Covid-19. Beyond vaccines, they also have application in gene therapy, offering potential to treat many currently incurable conditions including cancer, neurological disorders and cardiovascular diseases. However, much is still unknown regarding how the fundamental components of mRNA manufacturing systems (the RNA Polymerase and DNA template) mechanistically interact to determine product yield and quality. This is particularly true for the next-generation of mRNA therapeutics that are substantially larger and more complex than previously studied mRNA products. These products offer potential to improve patient outcomes by delivering enhanced therapeutic efficacies at reduced doses. However, we currently lack the required tools to optimise manufacture of these 'difficult-to-produce' molecules.

In this collaborative project with AstraZeneca, we will use a synthetic biology approach to design new biological components for production of next-generation mRNA therapeutics. This will include core synthetic biology techniques such as DNA sequence design, directed evolution of proteins, high-throughput screening of biological systems, bioanalytics, and machine learning.