Adeno-associated virus (AAV) has emerged as a leading platform for in vivo gene therapy, particularly in ocular diseases. AAV-based therapies are characterized by low pathogenicity and broad tissue tropism and have demonstrated clinical success, as exemplified by voretigene neparvovec-rzyl (Luxturna) being the first gene therapy to be approved by the U.S. Food and Drug Administration to treat RPE65-associated Leber congenital amaurosis (LCA). However, several challenges remain in the development of AAV-based gene therapies, including immune responses, limited cargo capacity, and the need for enhanced transduction efficiency, especially for intravitreal delivery to photoreceptors and retinal pigment epithelium cells. This review explores the biology of AAVs in the context of gene therapy, innovations in capsid engineering, and clinical advancements in AAV-based ocular gene therapy. We highlight ongoing clinical trials targeting inherited retinal diseases and acquired conditions, discuss immune-related limitations, and examine novel strategies for enhancing AAV vector performance to address current barriers.

中文翻译：

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重组腺相关病毒作为眼部基因治疗的递送平台：综合综述


腺相关病毒 （AAV） 已成为体内基因治疗的领先平台 ，尤其是在眼部疾病中。基于 AAV 的疗法具有致病性低和组织嗜性广的特点，并已证明临床成功，例如，voretigene neparvovec-rzyl （Luxturna） 是第一个被美国食品和药物管理局批准用于治疗 RPE65 相关 Leber 先天性黑朦 （LCA） 的基因疗法。然而，基于 AAV 的基因疗法的开发仍然存在一些挑战，包括免疫反应、有限的货物容量以及需要提高转导效率，尤其是玻璃体内递送到光感受器和视网膜色素上皮细胞。本综述探讨了 AAV 在基因治疗背景下的生物学、衣壳工程的创新以及基于 AAV 的眼部基因治疗的临床进展。我们重点介绍了正在进行的针对遗传性视网膜疾病和获得性疾病的临床试验，讨论了免疫相关的局限性，并研究了提高 AAV 载体性能以解决当前障碍的新策略。