Advances in RPGR gene therapy for X‑linked retinitis pigmentosa: From preclinical insights to clinical application (Review).

Abstract

X‑linked retinitis pigmentosa, primarily caused by mutations in the() gene, represents one of the most severe forms of inherited retinal degeneration, with early onset and rapid progression. Conventional interventions, such as vitamin A or docosahexaenoic acid supplementation, offer limited benefits and fail to halt disease progression. By contrast, gene therapy has emerged as a promising approach to alter the disease course. The present review summarizes the clinical phenotypes and pathogenic mechanisms associated withmutations, focusing on their disruption of ciliary transport and metabolic homeostasis. The present review further discusses advances in preclinical models, including mice, dogs, zebrafish and induced pluripotent stem cell‑derived organoids, that have facilitated the development of‑targeted therapies. Adeno‑associated virus‑based gene replacement has shown efficacy in restoring retinal structure and function, and several approaches have progressed to early‑phase clinical trials. Despite encouraging outcomes, challenges such as RPGR coding sequence instability, vector delivery efficiency and long‑term safety remain. The present review integrates current mechanistic understanding and therapeutic progress, providing a translational perspective for precision treatment of‑associated retinal diseases.