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Review
. 2024 Dec 4;32(12):4185-4207.
doi: 10.1016/j.ymthe.2024.10.017. Epub 2024 Oct 28.

Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review

Jiang-Hui Wang  1 , Wei Zhan  2 , Thomas L Gallagher  3 , Guangping Gao  4
Affiliations
Review

Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review

Jiang-Hui Wang et al. Mol Ther. .

Abstract

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.

Keywords: AAV; adeno-associated virus; capsid engineering; immune response; inherited retinal diseases; ocular gene therapy.

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Conflict of interest statement

Declaration of interests G.G. is a scientific co-founder of Voyager Therapeutics, Adrenas Therapeutics, and Aspa Therapeutics, and holds equity in these companies. G.G. is an inventor on patents with potential royalties licensed to Voyager Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies.

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