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

这个小企业技术转移(STTR)第一阶段项目的更广泛的影响/商业潜力是，拟议的交付系统将推动许多RNA治疗解决方案，以解决内膜增生(IH)和其他血管疾病。血管疾病是美国最常见的疾病病理，每年给美国的医疗系统造成超过4370亿美元的损失。由于血管干预的长期成功有限，因此迫切需要有效的治疗方法，包括解决介入后可能导致再狭窄或动脉狭窄的IH的情况。通过将治疗药物安全有效地输送到特定的组织，建议中的技术将提高生活质量，降低发病率，并与接触研究组织的商业模式相结合，将有助于促进多种针对血管系统和最终身体其他地区的RNA治疗药物的发展。最终，该平台将有助于广泛的RNA药物的开发和商业化，在科学、销售和制造领域创造就业机会。该项目将改善目前缺乏有效治疗的各种疾病和状况的治疗，从而提高生活质量，降低更广泛社会的发病率。这项小型企业技术转移(STTR)第一阶段项目旨在开发一种新型多功能脂质纳米颗粒(LNP)递送系统，用于组织特异性RNA疗法的血管系统靶向递送。血管内膜增生(IH)是一种由血管机械损伤引发的疾病，在介入治疗12个月后，约60%的外周血管疾病患者会导致动脉增厚。医院感染往往导致需要额外的手术干预，相关的费用和增加患者的发病率和死亡率。该项目将专注于通过直接输送到损伤部位的RNA治疗药物来抑制导致IH的重塑途径。该项目将开发血管靶向脂质体，旨在展示多功能潜力，靶向特定于血管病理区域的暴露胶原基质，并增强靶向血管摄取/输送。第一阶段将推进LNP技术，展示由该系统封装的积极治疗药物被适当地输送并产生临床相关的药物浓度。如果成功地将生物活性RNA有效载荷输送到受损的血管组织，该技术将降低介入后并发症的风险，并减少血管重建的需要。最终，这种新颖的LNP包装和输送系统将为推进广泛的RNA疗法提供新的工具。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.