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

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/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。这种疗法可以帮助人们保持开车、处理财务、看到亲人的面孔和独立生活的能力，从而防止视力和独立性的丧失。这不仅会提高黄斑变性患者的生活质量，而且还会减少美国医疗保健系统中视力障碍的经济负担。拟议中的疗法是一种持久的治疗方法，可能会持续一生，并且可以通过办公室手术进入眼睛。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需求。这项小型企业创新研究（SBIR）第一阶段项目旨在优化设计和所需剂量，以安全达到理想的表达水平，并从光诱导的视网膜变性中获得泛视网膜保护。拟议的aav介导的修饰剂疗法是一种表观遗传调节剂，它调节参与神经干细胞更新的基因表达，而不是取代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递送衣壳优化的各种测试，该衣壳将递送一种表观基因，作为表观遗传调节剂，增强先天抗氧化基因，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一期研究中，我们将进行体外（视网膜色素上皮细胞）和体内实验，以确定治疗的剂量、安全性和有效性，用于后续研究。该奖项反映了美国国家科学基金会的法定使命，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。

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.