STTR Phase I: Formulation of a COVID-19 mRNA Vaccine by Inverse Flash NanoPrecipitation

The broader impact/commercial potential of this this Small Business Technology Transfer (STTR) Phase I project is the development of a novel messenger ribonucleic acid (mRNA)-based vaccine for COVID-19. The fastest-to-clinic vaccine for COVID-19 was mRNA-based; however, there are no mRNA-based vaccines on the market currently. This is, in part, because this class of vaccines is difficult to optimize and manufacture at a large scale. If clinical trials are successful, hundreds of millions of doses will be needed in the U.S. alone. This STTR project aims to pioneer a novel technique to manufacture mRNA-based vaccines initially for COVID-19. This technology is highly modular, allowing for the better understanding and optimization of this class of vaccines. Importantly, this new technique can be scaled to manufacture the doses needed both for the current COVID-19 pandemic and in the case of future outbreaks. The flexibility and scalability of this platform technology provide a durable competitive advantage. Following demonstration of preclinical efficacy, the company will work with an established pharmaceutical partner for testing and manufacturing. Capturing 5% of the U.S. COVID-19 vaccine market would bring an estimated $125 million in revenue. This is a beachhead market, and, once successful, the company will expand into other mRNA-based vaccine and therapeutic markets. This Small Business Technology Transfer (STTR) Phase I project aims to develop an mRNA-based nanoparticle vaccine for COVID-19 without the use of cationic materials. Current formulation methods require cationic lipids or polymers to form charge-based complexes with the anionic mRNA. Charge-based assembly limits the accessible nanoparticle surface chemistries, a feature crucial to directing which cell types will be transfected and the resulting immune response. Additionally, mRNA is only a minor component of the resulting formulations. The proposed formulation method decouples the mRNA encapsulation from the nanoparticle surface in a two-step process. The method does not require cationic materials, allowing for mRNA loadings up to 5-times higher than those achievable through other routes. However, mRNA transfection has not previously been demonstrated without the use of cationic materials. This will be achieved by completing three key milestones: (1) optimize mRNA encapsulation, (2) vary surface coatings to enhance dendritic cell uptake, and (3) demonstrate efficient cell transfection. A highly loaded nanoparticle formulation that can efficiently target and transfect dendritic cells is desired. Following the completion of this Phase I work, this formulation may be applied to a SARS-CoV-2 spike protein-coding mRNA to produce a COVID-19 vaccine. 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.