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

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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.