Research Project
10325330
Project Summary This SBIR Direct to Phase II project will develop the first affinity membrane for purifying mRNA with high capacity, selectivity, and throughput. mRNA medicines have the potential to address a wide variety of pathologies. FDA emergency use authorizations for two mRNA-based COVID-19 vaccines represent the dawning of a new era of mRNA therapies. However, a company pioneering mRNA medicines has revealed that the lack of high throughput purification processes is a major hurdle that must be addressed in the upscaling of industrial mRNA. Purilogics expects that commercialization of the proposed innovation will have a major impact on the development of mRNA medicines by providing high-throughput solutions to the purification challenges experienced at the discovery and industrial production scales. By reducing purification cycles from hours to minutes, the innovation will increase productivity and, by association, improve patient accessibility to mRNA vaccines and medicines. The products of this project will be first-in-market, prepacked affinity membrane multi- well plates and chromatography columns and cassettes that can rapidly isolate and purify mRNA drugs from in vitro transcription mixture. Competing products have low productivity because of the long residence times needed for purification. In addition, their capacities are extremely low for large size mRNA. In our initial study, we proved the feasibility of fabricating high productivity mRNA affinity membranes. Membrane chromatography column prototypes dramatically outperformed competing commercial products, and the productivity and reusability milestones exceeded the defined acceptance criteria for moving to Phase II. Our industry collaborator evaluated the prototypes using proprietary mRNA feed streams. The purifications were faster and attained higher mRNA recovery and similar purity compared to competing products. The Phase II aims are (i) to develop mRNA affinity membranes with increased capacity that enable reduced purification times for mRNA of all sizes; (ii) to finalize a scalable process for mRNA affinity membranes and develop prototypes, and (iii) to determine mRNA affinity membrane column operating ranges and conduct field research on prototypes through industry collaboration. In Specific Aim 1, we will systematically evaluate the roles played by synthesis conditions and membrane pore size on performance. In Specific Aim 2, we will establish a process to produce the membranes. We will fabricate a series of membrane columns, laterally fed cassettes, and multi-well membrane plate prototypes. In Specific Aim 3, Purilogics will collaborate with an industry leader to evaluate prototypes for capture step purification of mRNA at multiple scales (research/pilot/production). Market entry for new bioprocessing tools is prior to clinical phase II trials. With the majority of mRNA drugs in phase I and II clinical trials, the time to develop a high-productivity mRNA purification technology is now. The addressable market for prepacked mRNA capture-step chromatography products is expected to reach $200 million by 2026.
