Accessible and affordable: Investigation of novel 'self-amplifying' mRNA delivery as cost-effective vaccine platforms for addressing future Canadian pandemic preparedness and health emergencies.

Proving their worth in the COVID-19 pandemic, mRNA therapies have since been used against many diseases. While mRNA suffers from short lifespans once injected and require high dosages for effective benefit, both barriers are overcome with self-amplifying mRNA (saRNA), an evolution of mRNA that replicates within host cells after treatment. Due to this replication, saRNA lasts much longer in patients and results in more gene therapy from less material, while maintaining the excellent safety profile of mRNA technologies. However, both mRNA and saRNA require formulation within carrier molecules for effective use. These carriers are costly and require specialized cold storage, incurring massive energetic and monetary costs and limiting their distribution to remote communities. There is a need for innovations that will increase accessibility of gene therapies while reducing their financial and ecological cost. This proposal aims to characterize one such innovation: a first-of-its-kind library of saRNA platforms that do not need carriers. Known as the 'VLVsa' library, these platforms bypass carrier formulation by creating their own carriers once injected inside a patient. The Ilkow lab, of which I am a member of, developed a COVID-19 vaccine in 2023. The main problems with that vaccine platform were its inability to be rapidly modified in response to new viral strains and its requirement of specialized cold storage, issues that the VLVsa library is well-positioned to overcome. I will investigate the ability of the VLVsa library to generate immunity in mice against SARS-CoV-2 when carrying the same antigen used previously by my lab. Future work will improve upon the library - adapting their use as vaccines against other diseases such as influenza and cancer. The COVID-19 pandemic highlighted the need for Canadian innovations in pandemic preparedness. This study will establish VLVsa platforms as accessible, cost-effective tools against future health emergencies in Canada.