Grant: Project Grant

Vision loss due to degeneration of the retina is common across numerous diseases including retinitis pigmentosa, which includes a group of rare diseases caused by 3000 mutations to 70 genes. While these diseases could be treated with genetic strategies, there is only one product available and it treats just 2% of this population. A gene agnostic strategy is the holy grail of treatment strategies and the one that we are pursuing. The retina, at the back of eye, includes cells that receive light (the photoreceptors). We are particularly focused on keeping the photoreceptors alive to preserve vision. There are two types of photoreceptors - the rods and the cones. In retinitis pigmentosa, the rods die first, followed by the cones. By delivering the factor produced by rods that keeps cones alive (i.e., rod-derived cone viability factor, RdCVF), we hypothesize that we can preserve vision. To this end, we are pursuing 3 independent aims, which will advance knowledge towards clinical use in the design of a novel, slow release formulation for RdCVF: (1) To control the release of RdCVF, we will use computational models to identify binding ligands specific to RdCVF and then immobilize these on a biocompatible, injectable hydrogel to enable slow release of RdCVF; (2) To overcome the limited stability of RdCVF in the degenerating retina, we will use computational models to identify a more stable RdCVF. We will then express these mutant RdCVFs and test their efficacy in our slow release formulations in models of retinitis pigmentosa; (3) To determine the clinical utility of our gene agnostic strategy, we will test our novel RdCVF slow release formulations with both healthy and diseased human retinal organoids while gaining greater insight into the mechanism of RdCVF treatment. These innovations in biomaterials, protein therapeutic release and computational modeling will be advanced by highly qualified personnel (HQP) who will benefit from multidisciplinary training.