Development of CRISPR strategies to treat inherited retinal diseases

The research outlined in this fellowship application proposes to explore the basic mechanisms of gene editing in the retina, using CRISPR based approaches. We have already generated extremely promising preliminary data, which specifically shows how we have used CRISPR gene editing to correct a mutation in the murine Ush2a gene, which is a major cause of untreatable blindness in young people. We have also developed a novel gene therapy vector system using DNA minicircles that has the potential to revolutionize gene therapy approaches in future, because it overcomes the major size limit impediment of standard AAV vectors. Here we propose to build on these novel preliminary findings in order to gain insight into the mechanisms of endogenous gene correction and the regulation of ectopic gene expression. The experiments described herein represent three pipelines of discovery science that are needed to explore the basic mechanisms of gene editing in the retina. As a translational research group also running clinical trials, we also believe that we will be an optimal position to translate this research into new methods for treating inherited blindness in patients in future.