Establishing channelrhodopsin as a tool to restore visual function

描述（由申请人提供）：Eos Neuroscience，Inc.，在与该公司的学术合作伙伴的合作下，正在开发一种结合基因疗法和光学工程技术的新技术，以恢复因视网膜色素变性或视网膜相关性黄斑变性等光感受器疾病而失明的人的视力。我们公司希望这项技术能够广泛应用于美国和全世界患有这些使人衰弱和致盲疾病的公众。简而言之，Eos Neuroscience，Inc.正在创造一种技术，可以在光感受器死亡或不再起作用后恢复视网膜剩余细胞的光敏性，从而恢复视网膜对光刺激的反应能力。为此，我们正在使用腺相关病毒（AAV）创建一种递送机制，该机制已被证明在将基因递送到细胞中方面是安全有效的。我们将利用这种机制将通道视紫红质（ChR2），一种光敏蛋白质，进入视网膜的备用功能细胞。此外，我们正在努力获得必要的安全性和有效性数据，以获得美国食品和药物管理局（FDA）的认可，以便我们将来可以开始在人类受试者中测试这项技术。我们已经开始在小鼠中进行这项测试，并将继续评估生理和行为措施。因此，我们为我们的SBIR I期项目提出了以下具体目标：1）建立导致我们的转基因在视网膜双极细胞中最佳和最特异性表达的AAV血清型，2）使用生理学和行为学技术测量我们的基因治疗的功效，和3）使用组织学和免疫学测量评估我们的基因治疗的基本安全性。公共卫生相关性：视网膜色素变性（RP）和年龄相关性黄斑变性（ARMD）等感光性疾病正在成为失明的主要原因，影响全球约1500万人。目前的治疗方法针对的是单一的遗传缺陷，或者使用电刺激来恢复视觉功能，这两种方法都不能广泛应用于光感受器疾病。为此，Eos Neuroscience，Inc.将建立一种使用通道视紫红质（一种光敏蛋白）来恢复光感受器退化患者的光敏感性的技术，该技术可以广泛且准确地应用于这些疾病的治疗。

DESCRIPTION (provided by applicant): Eos Neuroscience, Inc., in collaboration with the company's academic partners, is developing a novel technology combining gene therapeutics and optical engineering techniques to restore the ability to see in people that are blind from photoreceptor diseases such as Retinitis Pigmentosa or Age-Related Macular Degeneration. It is the hope of our company that this technology will be widely applicable and available to the general public in the United States and worldwide that suffers from these debilitating and blinding diseases. In brief, Eos Neuroscience, Inc. is creating a technology that will restore photosensitivity in the remaining cells of the retina after the photoreceptors have died or are no longer functional, thus restoring the ability of the retina to respond to light stimulation. To this end, we are creating a delivery mechanism using an adeno-associated virus (AAV) that is proven safe and effective at delivering genes into cells. We will use this mechanism to get channelrhodopsin (ChR2), a light sensitive protein, into the spared, functioning cells of the retina. Additionally, we are working towards the required safety and efficacy data necessary to gain acceptance from the Food and Drug Administration (FDA) so that we can begin testing this technology in human subjects in the future. We have started this testing in mice and will continue to evaluate both physiological and behavioral measures. Accordingly, we propose the following specific aims for our SBIR Phase I project: 1) establish the AAV serotype(s) that lead to the best and most specific expression of our transgene in retinal bipolar cells, 2) measure efficacy of our gene therapy using both physiological and behavioral techniques, and 3) evaluate the basic safety of our gene therapy using histological and immunological measures. PUBLIC HEALTH RELEVANCE: Photoreceptor diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (ARMD) are becoming leading causes of blindness, affecting approximately 15 million people worldwide. Current therapies are targeting single genetic defects or are using electrical stimulation to restore visual function - neither of which is capable of being a treatment that can be applied broadly to photoreceptor disease. To this end, Eos Neuroscience, Inc. will establish a technology using channelrhodopsin, a light sensitive protein, to restore light sensitivity in patients suffering from photoreceptor degeneration, a technology that can be applied broadly and accurately for the treatment of these diseases.