Grant: Project Grant

Aniridia is a rare eye disorder caused by half the normal amount of the protein paired box gene 6 (PAX6). It affects both sexes and is not known to be influenced by gender. Individuals with aniridia are typically born with low vision, and because there is no effective treatment, subsequently lose all vision. Thus, there is a therapeutic window available to prevent vision loss. This application will take advantage of recent advances in the fields of both traditional gene therapy and CRISPR gene therapy. Traditional "augmentation" gene therapy methods allow us to directly increase the amount of missing protein in affected cells to treat disease. CRISPR gene therapy allows us to modify DNA in affected cells to alter the behavior of the cells and treat disease. The broad goal of this proposal is to develop a gene therapy to treat patients with aniridia and to engage with the aniridia patient community. We hypothesize that using both traditional gene therapy and CRISPR gene therapy we can increase the amount of PAX6 protein and improve eye function in a mouse model of aniridia. We will also undertake a patient engagement initiative, which will include an analysis of Canadian policies on gene sequencing, characterization of patient motivators and barriers to gene sequencing, and generate a fact sheet regarding sequencing for aniridia. This work builds on Dr. Simpson's expertise in both mouse models and aniridia, and Dr. Robillard's expertise in patient engagement. By the end of the proposal, we will have completed the preclinical work in mouse and positioned the therapy for commercial investment. In addition, we will have given the tools we developed to not-for-profit companies for world-wide availability to researchers. Finally, we will have disseminated a fact sheet illuminating issues surrounding patient engagement in future clinical trials.