SBIR Phase I: Preclinical Validation of an Ocular Antioxidant Enhancing Gene Delivery Vehicle to Target Dry Macular Degeneration

SBIR 第一阶段：针对干性黄斑变性的眼部抗氧化剂增强基因递送载体的临床前验证

• 批准号: 2111704
• 负责人: Ramaswamy Ramkumar
• 金额: $ 25.6万
• 依托单位: OCULOGENEX
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2021-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2111704&HistoricalAwards=false
• 关键词: SBIR; Phase; Preclinical; Validation; Ocular

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop and commercialize a gene therapy to reverse the effects of dry age-related macular degeneration in over 200 million people worldwide over the age of 50. This therapy may prevent loss of vision and independence by helping people retain their ability to drive, handle finances, see faces of loved ones, and live independently. Not only would this improve the quality of life in patients with macular degeneration, but it would also decrease the economic burden of visual disability on the US healthcare system. The proposed therapy is a durable treatment that can potentially last a lifetime and be delivered into the eye with an in-office procedure. No treatments currently exist for this disease. This technology will meet an unmet need for hundreds of millions of patients with no other treatment options. This Small Business Innovation Research (SBIR) Phase I project seeks to optimize the design and dose required to safely reach the retina with desired expression levels and elicit pan-retinal protection from light-induced retinal degeneration. The proposed AAV-mediated modifier therapy is an epigenetic regulator that modulates gene expression involved in neural stem cell renewal rather than replacing various genes associated with macular degeneration. The proposed SBIR Phase 1 technical plan addresses the various tests for optimization of the delivery capsid, which will deliver an episomal gene that acts as an epigenetic regulator and boosts innate antioxidant genes, reduces cellular senescence, repairs DNA damage, and increases the expression of anti-apoptotic genes in retinal cells. In this SBIR Phase 1 study, we will conduct in vitro (retinal pigment epithelium cells) and in vivo experiments to determine the dosage, safety and efficacy of the treatment for subsequent studies.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.

这个小型企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是开发和商业化一种基因疗法，以逆转全球超过2亿50岁以上人群的干性年龄相关性黄斑变性的影响。这种疗法可以通过帮助人们保持驾驶，处理财务，看到亲人的面孔和独立生活的能力来防止视力和独立性的丧失。这不仅可以改善黄斑变性患者的生活质量，还可以减轻视力残疾对美国医疗保健系统的经济负担。拟议的治疗是一种持久的治疗，可能持续一生，并通过诊所手术进入眼睛。目前还没有针对这种疾病的治疗方法。这项技术将满足数亿没有其他治疗选择的患者的未满足需求。这个小型企业创新研究（SBIR）第一阶段项目旨在优化设计和所需的剂量，以安全地达到视网膜所需的表达水平，并引起全视网膜保护免受光诱导的视网膜变性。所提出的AAV介导的修饰剂疗法是一种表观遗传调节剂，其调节参与神经干细胞更新的基因表达，而不是替换与黄斑变性相关的各种基因。拟议的SBIR第1阶段技术计划解决了优化递送衣壳的各种测试，其将递送作为表观遗传调节剂并增强先天抗氧化基因的附加型基因，减少细胞衰老，修复DNA损伤，并增加视网膜细胞中抗凋亡基因的表达。在这项SBIR第一阶段研究中，我们将进行体外（视网膜色素上皮细胞）和体内实验，以确定后续研究的治疗剂量、安全性和有效性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。