[Advances on gene therapy for USH2A exon 13 related inherited retinal dystrophy]

Biallelic pathogenic variants in the USH2A gene result in Usher syndrome type Ⅱ and non-syndromic retinitis pigmentosa, both of which entail the progressive loss of photoreceptors leading to blindness. The cDNA of the USH2A gene is extensive, consisting of 15 606 base pairs, rendering it impractical for delivery via adeno-associated virus vectors for gene replacement therapy. Notably, exon 13 has emerged as a focal point for therapeutic intervention, given its predilection for harboring the most pathogenic variants within USH2A. Recent intervention studies targeting USH2A exon 13 through the utilization of antisense oligonucleotides, genome editing, and RNA editing approaches have exhibited promising therapeutic potential. This paper provides a comprehensive overview of the molecular mechanisms, outcome data, and the challenges associated with the application of these interventions in this domain.