Project No. 2492

Primary Supervisor

Prof Tobias von der Haar – University of Kent

Co-Supervisor(s)

Dr Ben Towler – University of Sussex

Prof Mark Smales – University of Kent

Dr Wei-Feng Xue – University of Kent

RNA Therapeutics are a new treatment modality that was very recently introduced into clinical use.

Its sole application at the moment is as vaccines, but hundreds of registered clinical trials currently explore other applications including cancer treatments, gene replacement for the treatment of hereditary diseases, and manipulation of receptor functions in patients to modulate eg inflammatory processes.

We have recently made strong progress in establishing foundational design principles for highly efficient mRNA Therapeutics. Although we can already reliably design sequences that result in highly efficient mRNAs, we are not yet able to control the secondary structure content of the designed mRNAs effectively and this limits our ability to fully explore the available design space. To address this, we have begun to establish a portfolio of methods allowing us to investigate the complex secondary structure landscape of mRNAs, which is dominated by fluid ensembles of structures rather than one structure with defined, stable elements. This PhD project applies and builds on this method portfolio in order to 1) fully characterise the distribution of secondary structures in our collection of mRNA Therapeutic sequences, and b) characterise how different secondary structural features determine the translatability and stability of mRNA Therapeutics in cultured cells.