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

STTR 第一期：用于血管 RNA 治疗靶向递送的多功能脂质纳米颗粒递送系统

• 批准号: 2309031
• 负责人: Richard Fisher
• 金额: $ 27.5万
• 依托单位: ORION THERAPEUTICS INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2309031&HistoricalAwards=false
• 关键词: STTR; Phase; Multifunctional; Lipid; Nanoparticle

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.

该小型企业技术转让 (STTR) 第一阶段项目的更广泛影响/商业潜力是，拟议的递送系统将推进许多 RNA 治疗解决方案，以解决内膜增生 (IH) 和其他血管疾病。血管疾病是最常见的疾病病理。在美国，该国医疗保健系统每年花费超过 4,370 亿美元，因为血管干预措施的长期成功有限，因此迫切需要有效的治疗方法，包括解决干预后可能发生的 IH 状况。通过安全有效地向特定组织提供治疗药物，可导致再狭窄或动脉狭窄，所提出的技术将提高生活质量并降低发病率，并与接触研究组织的商业模式相结合，将有助于推动疾病的发展。最终，该平台将有助于多种 RNA 药物的开发和商业化，从而在科学、销售和制造领域创造就业机会。治疗方面的改进目前缺乏有效治疗的多种疾病和病症，从而提高生活质量并降低更广泛社会的发病率。这个小型企业技术转让 (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) 输送系统用于向血管系统进行组织特异性靶向递送 RNA 治疗剂，内膜增生 (IH) 是一种由血管机械损伤引发的疾病，导致约 60% 的周围血管疾病患者在 12 个月内出现动脉增厚。 IH 通常会导致需要额外的手术干预，从而增加患者的发病率和死亡率。该项目将重点关注通过直接递送至损伤部位的 RNA 治疗来抑制导致 IH 的重塑途径。脂质体旨在表现出多功能潜力，可靶向特定于血管病理学区域的暴露胶原蛋白基质，并增强靶向血管摄取/输送，第一阶段将通过显示系统封装的活性治疗剂来推进 LNP 技术。如果成功地将生物活性 RNA 有效负载传递到受损的血管组织，该技术将降低干预后并发症的风险，并最终减少血运重建的需要。该系统将为推进广泛的 RNA 疗法提供新的工具。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。