AI Article Synopsis
- Adeno-associated virus (AAV) is a prominent platform for gene therapy, especially for eye diseases, due to its low risk of causing illness and ability to target various tissues.
- The first FDA-approved gene therapy, Luxturna, treats a specific genetic condition related to vision loss (RPE65-associated Leber congenital amaurosis).
- Challenges in AAV gene therapies include immune reactions, limited capacity to deliver genes, and the need for improved efficiency in delivering treatments to eye cells, leading to ongoing research and clinical trials for better outcomes.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638839 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2024.10.017 | DOI Listing |
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