STTR Phase I: Development of Thermostable Formulations of mRNA Vaccines and Therapeutics

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to overcome the cold-chain limitation for messenger ribonucleic acid (mRNA) therapy. Besides the COVID-19 mRNA vaccines developed by Moderna and Pfizer, many other mRNA vaccines and drugs are under development for treating cancers and infectious diseases, gene therapy, and cell therapy. The average global revenue of mRNA therapy in the next decade is projected to be ~$18 billion annually. One main bottleneck for the distribution of mRNA therapy products is the poor stability of the mRNA drug products, which results in high cold-chain costs, big wastage, and limited accessibility to rural areas. The thermostable mRNA formulation technology developed in this project will help pharmaceutical companies to save multi-billion dollars per year associated with low stability and expand the market to the rural US and tropical countries. The thermostable formulations will make the revolutionary mRNA vaccines and drugs accessible to the approximately 60 million rural population in the US and the approximately 3 billion people living in tropical countries without adequate cold-chain facilities. Expansion of the market will also lead to more affordable prices of mRNA therapy products for low-income, especially uninsured, families. This Small Business Technology Transfer (STTR) Phase I project will provide a low-cost and scalable solution to eliminate the cold-chain challenges in the distribution of mRNA active pharmaceutical ingredient (API) and mRNA lipid-nanoparticles (mRNA-LNPs) drug products. mRNAs and mRNA-LNPs in aqueous solutions undergo degradation through various pathways. Currently, the only way to increase their stability without freezing is to remove water by lyophilization, which requires additional facility, costs, time, and process development. This STTR Phase I project aims to test the feasibility to store the thermostable liquid formulations of mRNAs and mRNA-LNPs at room temperature for transportation and long-term storage. The research plan is designed towards two objectives: (1) To demonstrate mRNA APIs with various lengths in the optimized granule formulations retain >90% activity after transportation at 20ºC for more than two weeks; (2) To demonstrate that the optimized thermostable formulations of mRNA-LNP drug products retain >90% activity after storage at 20ºC for more than six months and 50ºC for up to 7 days during tropical outdoor transportation. Completing the Phase I project will provide the evidence to support that thermostability of the proprietary mRNA and mRNA-LNP formulations can meet the industrial requirement. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.