| Retinitis pigmentosa is the most common neurodegenerative disease that leads to blindness. The prevalence of RP in the United States is one in 4,000 individuals, affecting approximately 100,000 people. Worldwide, RP affects approximately 1.5 million individuals1. Autosomal dominant RP (adRP) has been documented to account for 40--54% of all RP cases, and although more than 80 genes have been associated with RP, mutations in the rhodopsin gene are responsible for nearly 50% of adRP1--5 . Due to the accessibility of the eye and genetic basis of RP, a gene therapy approach may be an attractive treatment option. Described herein are two approaches to alleviate RP using gene therapy. Zinc finger nucleases (ZFNs) present an opportunity to repair pathological mutations in the rhodopsin gene in a permanent fashion by harnessing the endogenous DNA repair process of homologous recombination following a targeted double strand break in the rhodopsin gene. MicroRNA-mediated rhodopsin gene suppression and replacement is also an attractive approach to treating RP, and was investigated using a novel murine model of RP expressing a pathological human rhodopsin on a mouse rhodopsin knockout background. This novel murine model provides advantages over previous models of RP and was used to investigate the efficacy of the microRNA gene suppression and replacement approach. The objective in these studies was to explore therapeutic intervention strategies for RP 6 with the ultimate goal of developing a viable treatment for this devastating disease. |
