PFI:AIR - TT: Molecular Artificial Retina For Vision Restoration After Photoreceptor Loss

PFI:AIR - TT：分子人工视网膜用于光感受器丧失后恢复视力

• 批准号: 1701257
• 负责人: Robert Chow
• 金额: $ 20万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1701257&HistoricalAwards=false
• 关键词: PFI; AIR; TT; Molecular; Artificial

This PFI: AIR Technology Translation project focuses on translating research on light-induced modulation of the activity of electrically excitable cells to fill the need for a treatment for the retinal degenerative diseases retinitis pigmentosa and dry age-related macular degeneration. The molecular artificial retina is important because over a million Americans suffer from advanced vision loss and this research has the potential to restore some level of vision in these patients, significantly improving quality of life. The project will confirm efficacy of the lead molecules based on ruthenium nanophotoswitches, evaluate their toxicity and optimize the scale up of the top candidates for pre-clinical and clinical trials of the molecular artificial retina. The nanophotoswitches (NPS) have the following unique features: it is a small molecule that is easily delivered (through injectable solutions or implants) to the eye, where it embeds in the membrane and ambient light activates neurons. The mechanism is universally applicable, both for any type of retinal degenerative disease and for any patient suffering from retinal degeneration. This is important, because many retinal degenerative diseases have multiple genetic components, making gene therapy complex and difficult. The class of molecules currently being investigated for a molecular artificial retina may be catalytic, therefore requiring only small, infrequent doses, and inexpensive, due to the simplicity of the system. These features provide the following advantages restoring vision with infrequent injections when compared to AREDs, a daily dose of vitamins that potentially delays the progression of the disease, the only FDA approved treatment in this market space.This project addresses the following technology gaps as it translates from research discovery toward commercial applications: Determine the biosafety of the lead NPS molecules and identify NPSs with low toxicity/ immunogenicity, evaluate therapeutic potential of the lead NPS, scale up the production of NPS to meet the market demand in quantity, and develop the polymer implant for sustained intraocular release of the NPS. In addition, personnel involved in this project, undergraduate students and postdoctoral scholars, will receive entrepreneurship and pharmaceutical/drug development experiences through customer discovery and collaborations with ophthalmologists conducting pre-clinical and clinical trials.

该PFI：AIR技术翻译项目专注于翻译关于电兴奋细胞活性的光诱导调制的研究，以满足视网膜变性疾病视网膜色素变性和干性年龄相关性黄斑变性的治疗需求。分子人工视网膜很重要，因为超过一百万美国人患有晚期视力丧失，这项研究有可能恢复这些患者的视力，显着提高生活质量。该项目将确认基于钌纳米光开关的铅分子的功效，评估其毒性，并优化分子人工视网膜临床前和临床试验的最佳候选人的规模。纳米光开关（nanophotoswitches）具有以下独特的功能：它是一种小分子，很容易（通过注射溶液或植入物）传递到眼睛，在那里它嵌入膜中，环境光激活神经元。该机制普遍适用于任何类型的视网膜变性疾病和任何患有视网膜变性的患者。这一点很重要，因为许多视网膜退行性疾病具有多种遗传成分，使得基因治疗变得复杂和困难。目前正在研究的用于分子人工视网膜的一类分子可能是催化剂，因此由于系统的简单性，仅需要小的、不频繁的剂量，并且便宜。与ARED相比，这些功能提供了以下优势，通过不频繁的注射恢复视力，ARED是一种每日剂量的维生素，可能会延迟疾病的进展，是该市场空间中唯一获得FDA批准的治疗方法。该项目解决了从研究发现到商业应用的以下技术差距：确定先导化合物分子的生物安全性，鉴定低毒性/免疫原性的NPS，评价先导化合物的治疗潜力，扩大先导化合物的生产规模以满足市场的大量需求，并开发用于眼内缓释的聚合物植入物。此外，参与该项目的人员，本科生和博士后学者，将通过客户发现和与进行临床前和临床试验的眼科医生合作获得创业和制药/药物开发经验。