STTR Phase II: Multifunctional Lipid Nanoparticle Delivery System for Targeted Delivery of Vascular RNA Therapeutics

The broader impacts/commercial potential of this Small Business Technology Transfer Research (STTR) Phase II project are the potential to advance RNA therapeutic solutions across a wide range of diseases. Safe and effective RNA delivery remains a critical challenge and the primary hurdle to clinical translation of RNA therapeutics. This project’s technology is intended to help RNA therapeutics clear this hurdle, facilitating the development of safe and effective targeted RNA therapeutics for diseases plaguing human health. Vascular disease interventions have limited long-term success, and there is a critical need for effective therapeutics; this project’s work for the treatment of intimal hyperplasia represents an important step toward the ultimate goal of improving the treatment of diseases currently lacking effective therapies. This project’s innovation will also contribute to the American economy by providing a combined product and CRO business model that will enhance the RNA therapeutic market, providing flexibility and a wide range of future applications for treatment of diseases across a wide range of potential partners. This project’s innovation will also promote the creation of American jobs in science sales and manufacturing. This Small Business Technology Transfer Research (STTR) Phase II project seeks to further develop a platform technology for targeted RNA therapeutic delivery. The widespread use of RNA therapeutics is challenged by the absence of safe, targeted, and effective solutions for delivery of the nucleic acid payload. This technology integrates customizable lipid nanoparticles that offer an improved delivery method for nucleic acid payloads incorporating one or multiple ligands to direct the system to specific tissue targets. After Phase I work demonstrated preliminary safety and efficacy in targeting injured cardiovascular vessel walls, this project will further validate the utilize the vascular targeted nanoparticles to further study and validate the dynamics of the platform. The RNA payload will be optimized to maximize gene silencing for therapeutic disease mitigation. Dosing regimens and local delivery will also be determined, along with key biomarkers for efficacy and safety monitoring. Further, manufacturing development will be conducted to facilitate manufacturing scaleup, and the targeting capabilities of the technology will be expanded to include myocardial healing applications. This work will promote the technology towards commercialization in the intimal hyperplasia arena, while also advancing the potential for future use in other applications. 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.