Sensing the protein interactome of a synthetic mRNA using solid-state nanopores to optimise mRNA therapeutics

Development of the therapeutic use of messenger RNA (mRNA) continues to intensify raising the need for novel analytical methods and optimisation strategies. This project looks at how the protein interactome of codon optimised, synthetic mRNA differs from endogenous mRNA. By expanding the current capabilities of solid-state nanopore sensing we will investigate protein-mRNA interactions of an in-development mRNA therapeutic for cardiac regeneration. This will reveal the impact of codon optimisation on successful binding of proteins important for translation and stabilisation. By reverse engineering the synthetic mRNA we will reinstate protein binding. This project will show the need for additional considerations in codon optimisation approaches, contribute to the optimisation of an in development therapeutic and develop nanopore sensing for implantation into the biophysical toolbox of RNA analysis.