Engineering a Sugar-targeted Nucleic Acid delivery Polymer to understand and enhance vaccination by self-amplifying RNA

"I aim to expand the broad clinical potential of self-amplifying RNA (saRNA) vaccines by crafting nanomaterial formulations that will target intracellular delivery of saRNA and molecular adjuvants to the key cells that mediate immunity. Both the devastating SARS-CoV-2 pandemic and annual flu seasons expose a significant need for more rapid development of effective vaccines. Nucleic acids such as self-amplifying messenger RNA (saRNA) are an exciting new class of subunit vaccine cargoes that promise to address the need for more adaptable, scalable, and more efficacious vaccines in comparison to those rooted in laboriously produced recombinant proteins. Although saRNA-based vaccine production offers a powerful platform to address these major issues with vaccine development, there is a huge need for innovative methods that can deliver nucleic acids across the body's many physiological barriers and generate protective immunity. This project seeks to apply the materials expertise of the applicant and the Stevens group (Imperial College London [ICL]) to the improved delivery and function of first generation saRNA vaccines that have been pioneered in the Shattock group (ICL). We hypothesize that polymer nanomaterial design can enable delivery of saRNA vaccine components to key cells responsible for generating adaptive immune responses and that this ""targeted"" saRNA vaccine delivery will lead to enhanced protective immunity compared to current vaccines. I will apply advanced polymerization techniques to tailor the delivery of saRNA to antigen presenting cells and to master cutting-edge imaging techniques to characterize the cellular response to targeted vaccine uptake (Raman, FIB-SEM). I will then collaborate with the Shattock lab to evaluate vaccine targeting in mice in vivo and in human skin explant models ex vivo, and complete a secondment at AstraZeneca that will provide invaluable insight into translational development of nanomaterials for nucleic acid delivery."