The promising clinical results obtained for ocular gene therapy in recent years have paved the way for gene supplementation to treat recessively inherited forms of retinal degeneration. We used spliceosome-mediated RNA trans-splicing as a strategy for repairing the transcript of the rhodopsin gene, the gene most frequently mutated in autosomal dominant retinitis pigmentosa (RP). Retinitis pigmentosa is characterized by a progressive degeneration of rod photoreceptors, leading to night-blindness and constriction of the visual field, followed by the degeneration of cone photoreceptors, resulting in a total loss of vision. In this study, we demonstrated the repair of dominant mutations of RHO by RNA trans-splicing. Using two different cellular models of RHO expression, we showed that a significant proportion—up to 40%—of the mRNA could be repaired, leading to an improvement of the phenotype, characterized by correction of the subcellular distribution of RHO.
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