Efficacy and Safety of Transcriptional Repressors as Biotherapeutics for the Treatment of Autosmal Dominant Retinitis Pigmentosa (ADRP)

We recently described a method to turn-off the expression of a disease gene, which cause autosomal dominant Retinitis Pigmentosa (adRP). The strategy employed is based on the use of artificial proteins (artificial transcriptional repressors) capable to bind DNA regulatory sequences of the rhodopsin gene and block its expression. The system thus far created, although efficacious, is specific for human rhodopsin DNA sequences and thus, it is difficult its further development and testing in animal models. In the present project we propose design and test novel artificial proteins with the ability to bind rhodopsin regulatory sequences of different animal-species. The generation of these universal rhodopsin switch will enable to test in relevant animal model whether the rhodopsin gene can be turned-off (in mutational independent manner) and whether simultaneous replacement of the mutated copy with a correct one results in correction of the retinal defect.