Mutation-Independent Gene Therapies for Rod-Cone Dystrophies

Abstract

The clinical success of gene replacement therapies in recent years has served as a proof of concept for the treatment of inherited retinal degenerations using adeno-associated virus (AAV) as viral vector. However, inherited retinal degenerative diseases showcase a broad genetic and mechanistic heterogeneity, challenging the development of mutation-specific therapies for each specific mutation. Mutation-independent approaches must be developed to slow down retinal degeneration regardless of the underlying genetic mutation and onset of the disease. New understanding of cell death mechanisms in rod-cone dystrophies have led to promising rescue of photoreceptor cell death by virally mediating expression of anti-apoptotic factors and secretion of retinal neurotrophic factors. Optogenetic therapies are also able to restore light sensitivities in blind retinas.

Keywords: Adeno-associated virus; Apoptosis; Cell death; Gene therapy; Mutation-independent; Müller glia; Neuroprotection; Optogenetics; Photoreceptor; Retinitis pigmentosa.