Demonstration of POC of a PAX6 saRNA in a model of PAX6 driven Aniridia.

在 PAX6 驱动的 Aniridia 模型中演示 PAX6 saRNA 的 POC。

• 批准号: 10028371
• 金额: $ 41.1万
• 依托单位: MINA THERAPEUTICS LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10028371
• 关键词: Demonstration; POC; PAX6; saRNA; model

Aniridia is a rare disease where patients' eyes develop improperly due to a genetic mutation in a gene called PAX6\. Although rare, the disease has a dramatic detrimental impact of patients' quality of life. Importantly, although the patients are born with eye problems, the worst aspects of disease occur later in life. The biggest problem occurs in the teens and early twenties when the transparent front part of the eye, the cornea, begins to fail leading to extensive pain, inflammation and loss of transparency. At present, the only options are surgery to transplant healthy cornea and this complicated intervention only provides temporary relief. In this project we will build upon our ongoing work to develop a new treatment based on gene activation technology that we anticipate will dramatically improve patients' lives and reduce their requirement for complicated clinical care.This project is led by MiNA therapeutics who are world-experts at using a new class of drug known as "RNA activation". Here we will use all our knowledge in using RNA activation to rescue expression of the PAX6 gene. We have been working on this project with clinician scientists and molecular biologists at the University of Liverpool for the past 4 years and are now in position with a candidate molecule that we are confident works effectively in cells. In this project, we will confirm this finding in more relevant model systems as the final step before initiating preclinical studies and human clinical trials.Specifically, this project will involve making a series of targeted changes to our lead candidate to make it more effective, more stable and more potent, and to ensure we can deliver the drug to the appropriate cells in the eye. We will then use a mouse model of aniridia that is widely used and has been thoroughly characterised and is very similar to the human disease. Using this model, we will test our new drugs, determining the optimal dose and delivery approaches.

无虹膜症是一种罕见疾病，患者的眼睛由于 PAX6 基因突变而发育不良。尽管罕见，但这种疾病对患者的生活质量具有巨大的不利影响。重要的是，尽管患者生来就有眼部问题，但疾病最严重的方面却发生在以后的生活中。最大的问题发生在青少年和二十岁出头，此时眼睛的透明前部角膜开始衰竭，导致广泛的疼痛、炎症和透明度丧失。目前，唯一的选择是手术移植健康的角膜，这种复杂的干预措施只能暂时缓解症状。在这个项目中，我们将在我们正在进行的工作基础上开发一种基于基因激活技术的新疗法，我们预计这种疗法将显着改善患者的生活并减少他们对复杂临床护理的需求。该项目由世界级专家 MiNA Therapeutics 领导。使用一种称为“RNA激活”的新型药物。在这里，我们将利用我们所有的知识来利用 RNA 激活来挽救 PAX6 基因的表达。过去 4 年里，我们一直与利物浦大学的临床科学家和分子生物学家合作开展这个项目，现在已经找到了一种候选分子，我们相信它可以在细胞中有效发挥作用。在这个项目中，我们将在更相关的模型系统中确认这一发现，作为启动临床前研究和人体临床试验之前的最后一步。具体来说，这个项目将涉及对我们的主要候选药物进行一系列有针对性的改变，使其更有效、更有效。稳定且更有效，并确保我们能够将药物输送到眼睛中的适当细胞。然后，我们将使用广泛使用的无虹膜小鼠模型，该模型已被彻底表征，并且与人类疾病非常相似。使用这个模型，我们将测试我们的新药，确定最佳剂量和给药方法。