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Abstract：
Inherited retinal diseases (IRDs) encompass a diverse group of genetic disorders that lead to progressive visual impairment and blindness. Over the years, considerable strides have been made in understanding the underlying molecular mechanisms of IRDs, laying the foundation for novel therapeutic interventions. Gene therapy has emerged as a compelling approach for treating IRDs, with notable advancements achieved through targeted gene augmentation. However, several setbacks and limitations persist, hindering the widespread clinical success of gene therapy for IRDs. One promising avenue of research is the development of new genome editing tools. Cutting-edge technologies such as CRISPR-Cas9 nucleases, base editing and prime editing provide unprecedented precision and efficiency in targeted gene manipulation, offering the potential to overcome existing challenges in gene therapy for IRDs. Furthermore, traditional gene therapy encounters a significant challenge due to immune responses to viral vectors, which remain crucial obstacles in achieving long-lasting therapeutic effects. Nanotechnology has emerged as a valuable ally in the quest to optimize gene therapy outcomes for ocular diseases. Nanoparticles engineered with nanoscale precision offer improved gene delivery to specific retinal cells, allowing for enhanced targeting and reduced immunogenicity. In this review, we discuss recent advancements in gene therapy for IRDs and explore the setbacks that have been encountered in clinical trials. We highlight the technological advances in genome editing for the treatment of IRDs and how integrating nanotechnology into gene delivery strategies could enhance the safety and efficacy of gene therapy, ultimately offering hope for patients with IRDs and potentially paving the way for similar advancements in other ocular disorders.
摘要：
遗传性视网膜疾病(IRD)包括导致进行性视力损害和失明的多种遗传性疾病。多年来,在理解IRD的潜在分子机制方面已经取得了相当大的进展，为新型治疗干预奠定基础。基因治疗已经成为治疗IRD的一种引人注目的方法，通过靶向基因增强实现了显著的进步。然而,一些挫折和局限性仍然存在，阻碍了IRD基因治疗的广泛临床成功。一个有希望的研究途径是开发新的基因组编辑工具。尖端技术，如CRISPR-Cas9核酸酶，碱基编辑和主要编辑在靶向基因操作中提供了前所未有的精度和效率，提供了克服IRD基因治疗现有挑战的潜力。此外，由于对病毒载体的免疫反应，传统的基因治疗面临着重大挑战，这仍然是实现持久治疗效果的关键障碍。纳米技术已成为寻求优化眼部疾病基因治疗结果的有价值的盟友。具有纳米级精度的纳米颗粒为特定的视网膜细胞提供了改进的基因递送，允许增强的靶向性和降低的免疫原性。在这次审查中,我们讨论了IRD基因治疗的最新进展，并探讨了临床试验中遇到的挫折。我们强调了用于治疗IRD的基因组编辑技术的进步，以及将纳米技术整合到基因传递策略中如何提高基因治疗的安全性和有效性。最终为IRD患者带来希望，并可能为其他眼部疾病的类似进展铺平道路。
