Introduction: Clinical Context and Unmet Need in X-Linked Retinitis Pigmentosa
X-linked retinitis pigmentosa (XLRP) is a severe inherited retinal dystrophy characterized by progressive photoreceptor degeneration leading to night blindness, peripheral vision loss, and eventual blindness. Mutations in the RPGR gene, particularly in the ORF15 isoform, account for the majority of XLRP cases. The RPGR ORF15 region, however, is notoriously difficult to clone and express due to its repetitive, unstable sequence prone to secondary structures and cryptic splicing, which historically has posed significant challenges to gene replacement therapy development. Existing treatment strategies remain largely supportive, underscoring the critical unmet need for effective molecular therapies that halt or reverse photoreceptor degeneration in XLRP patients.
