Grant: CIHR REDI Early Career Transition Award - General

Gene therapy is a rapidly growing field that offers hope for previously untreatable diseases by modulating the biological activity or replacing a defective gene. Gene therapy relies on the delivery of nucleic acids, such as messenger RNA (mRNA) and lipid nanoparticles (LNP) have emerged as the most suitable carrier for RNA. Their utility is exemplified by the clinical success of Onpattro in a rare disease known as transthyretin induced amyloidosis and the COVID-19 mRNA vaccine. Despite these initial successes, the wider use of LNP-mRNA against diseases that could benefit from gene therapy, including cancer, is limited due to the safety and effectiveness concerns with the current LNP formulation. Improving the design of LNP-mRNA is crucial for realizing their full potential in clinical settings. My research proposal aims to develop the next generation of LNP-based genetic medicines by (1) creating a library of LNP with optimize features that improve effectiveness, (2) derive the principles of lipid-mRNA interaction that protects mRNA function and (3) combine modified LNP-mRNA and light to trigger the delivery of mRNA more effectively and safely for cancer treatment.