GET-READY: Genetic therapy for EYS- and USH2A-associated retinal disease

The retina is a tissue that lines the back of the eye, and is responsible for receiving, modulating and transmitting the incoming light signal to the brain for image interpretation. A disruption in any of these steps can result in visual impairment. An important cause of vision loss is mutations in one of many genes important for retinal structure and function. Such mutations cause the retina to degenerate over time and give rise to a group of rare diseases collectively named inherited retinal diseases (IRDs). Although there is no definitive cure, there has been much progress made over the last ten years in terms of genetic therapies. In particular, gene augmentation therapy, which consists of introducing a healthy copy of the mutated gene into the patient’s retina, has proven the most promising and has even been approved for the treatment of IRD due to mutations in one gene. This approach however is not applicable to genes exceeding the size of the currently used gene vehicles, including two of the most frequently mutated genes, EYS and USH2A. The aim of our proposal is to address these current limitations. We will develop alternative therapeutic approaches, and in parallel optimise novel larger vehicles that can ensure a proper delivery of EYS and USH2A coding sequences to the retina. If successful, our project will result in the treatment of a non-negligible patient population, and consequently improve the life-quality of these patients as well as reduce the socio-economic burden due to progressive vision loss.