I-Corps: Thermostable liquid formulations of mRNAs and mRNA lipid nano-particles pharmaceuticals

University Of North Carolina At Wilmington, Wilmington NC

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is the development of an RNA formulation technology for safe storage and transport. The ability to transport and store mRNA-based pharmaceuticals without ultra-cold requirements may significantly lower the costs of distribution of mRNA drugs and vaccines. Also, elimination of the requirements for ultra-freezer and lyophilization will greatly increase the capacity and speed of deployment of mRNA pharmaceuticals as well as their accessibility to remote areas. Finally, the superior thermostability of the new mRNA formulations may reduce the wastage of drugs/vaccines caused by unexpected exposure to elevated temperature during transportation and storage. This I-Corps project is based on the development of two methods for preparing thermostable liquid formulations of mRNA and mRNA-Lipid Nano-Particles (LNPs), respectively. The first method is to prepare an emulsion containing mRNA condensate-induced non-ionic polymers and salts. The second method is to stabilize mRNA-LNPs using acidic buffers with crowding agents. The success of the COVID-19 mRNA vaccines showed the advantages of this pharmaceutical modality including rapid development, high efficacy, high safety, and ease of manufacturing (as compared to cell culture production). However, deployment of the COVID-19 mRNA vaccines has been met with major logistic challenges due to the intrinsic instability of mRNA. mRNAs undergo fast degradation in aqueous solutions and require freezing or lyophilization (freeze-drying) for transportation and storage. The requirements for ultra-cold chain or lyophilization facilities not only limit the speed of deployment and accessibility of mRNA pharmaceuticals, but also increase the costs and wastage during the distribution process. Using the proposed technologies, mRNA or mRNA-LNP solutions may be able to be stored at room temperature or under refrigeration for months without freezing or lyophilization. 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.