Grant: Alliance Grants

The COVID-19 pandemic resulted in an explosion of mRNA-based technologies. It became evident that mRNA-based applications go far beyond vaccination strategies. Indeed, the delivery of mRNA to target organs and tissues can serve as a valuable tool for expressing proteins of interest in many aspects of life sciences. One of the most challenging drawbacks of mRNA-based approaches is that mRNA is highly unstable and susceptible to degradation. Such degradation occurs during production phases, storage, and in organisms after delivery. Therefore, there is an urgent need for the development of mRNA stabilization technologies that will facilitate mRNA use in various aspects of life sciences. In this application, we propose developing a new mRNA stabilization procedure based on the deuteration of mRNA during the production and storage phases. The application of deuterium in animal biology was shown to be non-toxic, safe, and effective. In specific objective one, we will establish protocols for mRNA stabilization and assess the outcomes during the production and storage phases. In specific objective two, we will characterize mRNA degradation in cell culture and mice. Furthermore, we will confirm that the resulting mRNA can enter protein translation cellar machinery and translated into functional proteins in vitro and in vivo. In conclusion, the results of this proposal will help the development of safe mRNA products, which will enable the participating industrial partners to enter the global market of mRNA therapeutics. Furthermore, during the five-year term of this proposal, we will train more than twenty highly qualified personnel who will join the Canadian workforce in the rapidly growing fields.