Prime Editing
Prime editing is a novel precision gene correction technique that can be applied to correct virtually any mutation. In this project, we aim to correct the most common mutations in the USH2A and EYS genes. The genetic repair of the mutations expected to provide a therapeutic benefit. In order to facilitate translation of this concept to the clinic, we will apply disease models that are closely related to the living human eye, including human engineered retinal organoids. We engineer these organoids so that they contain the USH2A and EYS mutations. To deliver the prime editors to retinal cells, we will apply the adeno-associated vectors (AAV) platform. AAVs have been shown to be effective and well tolerated in the eye after subretinal injection. Importantly, prime editing can potentially correct 95% of all human mutations and if this project is successful, theoretically other mutations can be corrected with only slight changes in the therapeutic construct. The idea of potential correction of an underlying genetic problem in vivo is unprecedented in biomedicine and the fact that this strategy could reasonably reach the clinic within 5-6 years provides an exceptional opportunity.
