Geiger A B, Kennedy J G, Staker L G, Wensel T G, Casson R J, Thomas P Q
Discipline of Reproduction and Development, School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute (SAHMRI), Australia; Robinson Research Institute (RRI), The University of Adelaide, Adelaide, SA, Australia.
Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Prog Retin Eye Res. 2025 Jul;107:101376. doi: 10.1016/j.preteyeres.2025.101376. Epub 2025 Jun 6.
Inherited retinal diseases (IRDs), such as retinitis pigmentosa, are a heterogenous group of genetic eye diseases characterized by degeneration of photoreceptors. They are the leading cause of blindness in the working age population in high-income countries and are an ideal target for the expanding gene editing tool kit, including rapidly evolving CRISPR/Cas9 technology. In this review, we provide a comprehensive analysis of CRISPR/Cas9 technologies currently being explored as therapeutic interventions for IRDs. Given the challenges posed by the growing complexity and size of gene editing systems, the delivery of these therapeutics to the retina has necessitated innovative approaches. We review current delivery methods, including nanoparticles, virus-like particles and traditional viral vectors, highlighting their advantages and limitations. This review underscores the potential transformative impact of gene editing on genetic disease management, emphasising that advancements in these technologies, coupled with improved pre-clinical models, bring clinically safe and effective treatments for IRDs within view.
遗传性视网膜疾病（IRDs），如色素性视网膜炎，是一组异质性的遗传性眼病，其特征是光感受器退化。它们是高收入国家劳动年龄人口失明的主要原因，也是不断扩展的基因编辑工具包（包括快速发展的CRISPR/Cas9技术）的理想靶点。在本综述中，我们对目前作为IRDs治疗干预手段正在探索的CRISPR/Cas9技术进行了全面分析。鉴于基因编辑系统日益复杂和规模不断扩大所带来的挑战，将这些治疗方法递送至视网膜需要创新方法。我们回顾了当前的递送方法，包括纳米颗粒、病毒样颗粒和传统病毒载体，突出了它们的优点和局限性。本综述强调了基因编辑对遗传疾病管理的潜在变革性影响，强调这些技术的进步，再加上改进的临床前模型，使临床上安全有效的IRDs治疗方法指日可待。
