Retina-directed gene therapy: Achievements and remaining challenges

Biber, Josef; Gandor, Catharina; Becirovic, Elvir und Michalakis, Stylianos (July 2025): Retina-directed gene therapy: Achievements and remaining challenges. In: Pharmacology & Therapeutics, Vol. 271, 108862

Abstract

Gene therapy is an innovative medical approach that offers new treatment options for congenital and acquired diseases by transferring, correcting, inactivating or regulating genes to supplement, replace or modify a gene function. The approval of voretigene neparvovec (Luxturna), a gene therapy for RPE65-associated retinopathy, has marked a milestone for the field of retinal gene therapy, but has also helped to accelerate the development of gene therapies for genetic diseases affecting other organs. Voretigene neparvovec is a vector based on adeno-associated virus (AAV) that delivers a functional copy of RPE65 to supplement the missing function of this gene. The AAV-based gene delivery has proven to be versatile and safe for the transfer of genetic material to retinal cells. However, challenges remain in treating additional inherited as well as acquired retinopathies with this technology. Despite the high level of activity in this field, no other AAV gene therapy for retinal diseases has been approved since voretigene neparvovec. Ongoing research focuses on overcoming the current restraints through innovative strategies like AAV capsid engineering, dual-AAV vector systems, or CRISPR/Cas-mediated genome editing. Additionally, AAV gene therapy is being explored for the treatment of complex acquired diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) by targeting molecules involved in the pathobiology of the degenerative processes. This review outlines the current state of retinal gene therapy, highlighting ongoing challenges and future directions.

• Item Type: Journal article
• Faculties: Medicine > Medical Center of the University of Munich > Eye Clinic and Polyclinic
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 01637258
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 513025799