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

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is that the proposed delivery system will advance many RNA therapeutic solutions to address intimal hyperplasia (IH) and other vascular conditions. Vascular disease is the most common disease pathology in the US, costing the country’s healthcare system over $437 billion dollars annually. Because vascular interventions have limited long-term success, there is a critical need for effective therapeutics, including to address the condition of IH which, post intervention, can lead to restenosis, or artery narrowing. By delivering therapeutics safely and efficaciously to specific tissues, the proposed technology will result in improved quality of life and decreased morbidity and, in combination with a Contact Research Organization business model, will contribute to the advancement of a multitude of RNA therapeutics targeting the vascular system and eventually other areas of the body. Eventually, the platform will contribute to the development and commercialization of a broad range of RNA drugs, creating jobs in science, sales, and manufacturing. This project will lead to improvements in the treatment of a variety of diseases and conditions that currently lack effective therapy, resulting in improved quality of life and decreased morbidity in the broader society. This Small Business Technology Transfer (STTR) Phase I project seeks to develop a novel multifunctional lipid nanoparticle (LNP) delivery system for tissue-specific targeted delivery of RNA therapeutics to the vascular system. Intimal hyperplasia (IH), a condition triggered by mechanical injury to blood vessels, causes artery thickening in ~ 60% of peripheral vascular disease patients 12 months post-intervention. IH often results in the need for additional surgical intervention with associated costs and increased patient morbidity and mortality. This project will focus on inhibiting the remodeling pathways that lead to IH via RNA therapeutics delivered directly to the injury site. The project will develop vascular targeting liposomes designed to exhibit multifunctional potential to target exposed collagen matrices specific to areas of vascular pathology and enhanced targeted vascular uptake/delivery. Phase I will advance the LNP technology by showing that an active therapeutic encapsulated by the system is appropriately delivered and results in a clinically relevant drug concentration. If successful at delivering bioactive RNA payloads to injured vascular tissues, the technology will reduce the risk of post-intervention complications and reduce the need for revascularization. Ultimately, this novel LNP packaging and delivery system will provide a new tool for advancing a broad range of RNA therapeutics. 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.