Gene Therapy for Inherited Retinal Diseases: From Genome Editing to Next-Generation Delivery Systems

Inherited retinal diseases (IRDs) represent a heterogeneous group of rare genetic disorders that, despite their low prevalence, contribute significantly to blindness in children and adults worldwide. With over ۲۸۰ causative genes identified, our understanding of the molecular basis of these diseases has substantially deepened; however, the development of effective treatments remains challenging due to genetic diversity and the complex structural organization of the retina. Gene therapy, particularly with the emergence of the CRISPR-Cas۹ system and advanced methods such as base editing and prime editing, has opened new horizons for targeted mutation correction. Nevertheless, the efficient delivery of these therapeutic tools to retinal cells, especially post-mitotic photoreceptors and retinal pigment epithelium cells, remains a major obstacle. In this context, nanoparticles offer innovative solutions by overcoming anatomical barriers and providing targeting capabilities, thereby paving the way for safer and more effective therapeutic strategies. Three-dimensional retinal organoids derived from induced pluripotent stem cells have also emerged as valuable platforms for disease modeling and the evaluation of personalized therapeutic approaches. This analytical review comprehensively examines the recent advances and persistent challenges in IRD gene therapy and presents a perspective on integrated approaches for precision medicine.

کلیدواژه ها:

Inherited retinal diseases ، Gene therapy ، CRISPR-Cas۹ ، Base editing ، Nanoparticles ، Retinal organoids