Grant: Doctoral Research Award: Canada Graduate Scholarships

Messenger ribonucleic acids (mRNA) that are functional in the cytoplasm without the need to access the nucleus can be used but have a short half-life and reduced protein translation. Alternatively, the mRNA can be designed to contain proteins that make multiple copies at exponential rates, thus increasing the amount of protein produced from a small dose. Such mRNA constructs with replicative properties are called self-amplifying RNA (saRNA). Replicases that make the saRNA copies have traditionally been obtained from alphaviruses such as Venezuelan Equine Encephalitis. However, relying on one source of the replicase assumes that performance will be similar if the saRNA is used for vaccination against multiple antigens. Therefore, this project aims to expand the saRNA toolkit by surveying different viral families and their suitability to be sources of replicases. Novel saRNA vectors will be assessed in human skin explants obtained from donors after surgery. Using human skin explants as a model ensures we capture the interaction between different cells and the saRNA injected. saRNA designs deemed highly replicative and less toxic will be used in mice vaccine studies. This project will provide effective saRNA vectors to express antigens. Additionally, advancing the saRNA designs into clinical settings will result in cost-effective therapies due to low dosage owing to its capability to replicate in cells.