SBIR Phase I: Proof-of-concept of a customizable, next-generation RNA delivery particle

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the creation of a novel RNA drug delivery platform with implications for treatment of cancer and other various diseases with unmet medical need. Current delivery technologies fail to realize the potential of nucleic acid drugs because of limitations like target specificity, toxicity, and administration. Next generation delivery technologies are ultimately required to achieve the full therapeutic potential of nucleic acid drugs. The technology being developed in this project is designed to address the limitations of existing delivery modalities, resulting in a flexible platform with target- and cargo-customization ready for progression to evaluate multiple clinical disease targets. This will expand treatment options, initially for oncology targets, with further applications in gene editing and vaccines, and continue to address existing patient needs. The technology developed in this project has the potential to expand the nucleic acid delivery market and result in improvements to length and quality of life for individuals facing life-threatening diseases in multiple therapeutic areas in both the United States and globally. This Small Business Innovation Research (SBIR) Phase I project will address the proof-of-concept milestones required to validate delivery of RNA cargoes to target cells using an engineerable protein nanoparticle. The particle platform has several key attributes incorporated that enable efficient and targeted delivery, and which are required for full platform functionality: 1) the ability to package nucleic acid, 2) display of targeting moiety, and 3) the ability to disassemble within the intracellular environment and release nucleic acid cargoes. In this project, particles engineered to target specific cancer cell surface markers will be 1) in vitro loaded with mRNA cargoes, 2) evaluated in vitro for delivery of RNA cargoes to specific cancer cells, 3) evaluated in vivo for delivery of RNA cargoes to target tumors with exceptional specificity, and 4) evaluated in vivo for efficacy of therapeutic RNA delivery. The result of this project will be a validated customizable delivery platform positioned for clinical development against multiple targets. 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.