重组腺相关病毒作为眼部基因治疗的传递平台:全面回顾。

IF 12.1 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Molecular Therapy Pub Date : 2024-12-04 Epub Date: 2024-10-28 DOI:10.1016/j.ymthe.2024.10.017
Jiang-Hui Wang, Wei Zhan, Thomas L Gallagher, Guangping Gao
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引用次数: 0

摘要

腺相关病毒(AAV)已成为体内基因疗法,尤其是眼部疾病基因疗法的主要平台。基于 AAV 的疗法具有低致病性和广泛组织滋养性的特点,并已在临床上取得成功,例如,Luxturna 是美国食品和药物管理局批准的首个用于治疗与 RPE65 相关的 Leber 先天性无眼病(LCA)的基因疗法。然而,基于 AAV 的基因疗法的开发仍面临一些挑战,包括免疫反应、有限的载货能力以及提高转导效率的需要,尤其是在向光感受器和视网膜色素上皮细胞(RPE)进行玻璃体内递送时。本综述探讨了基因治疗背景下 AAV 的生物学特性、囊壳工程的创新以及基于 AAV 的眼部基因治疗的临床进展。我们重点介绍了针对遗传性视网膜疾病和获得性疾病正在进行的临床试验,讨论了与免疫相关的局限性,并研究了提高 AAV 载体性能以解决当前障碍的新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.

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.

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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
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