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.

Aniridia是一种罕见的疾病，患者的眼睛由于一个称为PAX6 \的基因中的基因突变而出现不当。尽管很少见，但这种疾病对患者的生活质量产生了巨大的有害影响。重要的是，尽管患者天生患有眼睛问题，但疾病最糟糕的方面发生在以后的生活中。最大的问题发生在青少年和二十多岁时，当时眼睛的透明前部部分开始失败，导致广泛的疼痛，炎症和透明度丧失。目前，唯一的选择是对健康角膜的手术进行手术，而这种复杂的干预只提供了暂时的缓解。在这个项目中，我们将基于我们正在进行的工作，以开发基于基因激活技术的新治疗方法，我们预计将大大改善患者的生活并减少对复杂临床护理的需求。该项目由Mina Therapeutics领导，这些项目是世界上使用一种新的药物使用称为“ RNA激活”的新型药物。在这里，我们将使用所有知识来利用RNA激活来挽救PAX6基因的表达。在过去的四年中，我们一直在利物浦大学与临床医生和分子生物学家一起研究这个项目，现在与候选分子保持适当的位置，我们对细胞有效工作有效。在该项目中，我们将在更相关的模型系统中确认这一发现是启动临床前研究和人类临床试验之前的最后一步。特别是，该项目将涉及对我们的主要候选人进行一系列有针对性的更改，以使其更有效，更稳定，更有效，并确保我们可以将药物运送到眼中适当的细胞。然后，我们将使用广泛使用且经过彻底表征的aniridia的小鼠模型，并且与人类疾病非常相似。使用此模型，我们将测试我们的新药，确定最佳剂量和递送方法。