AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.

Autor: Castro BFM; LVF Ophthalmology Research Centre, Translational Research Institute, Brisbane, QLD, 4102, Australia. b.castro@uq.edu.au.; Greenslopes Clinical School, University of Queensland School of Medicine, Brisbane, QLD, Australia. b.castro@uq.edu.au., Steel JC; LVF Ophthalmology Research Centre, Translational Research Institute, Brisbane, QLD, 4102, Australia.; Greenslopes Clinical School, University of Queensland School of Medicine, Brisbane, QLD, Australia.; School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, QLD, Australia., Layton CJ; LVF Ophthalmology Research Centre, Translational Research Institute, Brisbane, QLD, 4102, Australia. c.layton@uq.edu.au.; Greenslopes Clinical School, University of Queensland School of Medicine, Brisbane, QLD, Australia. c.layton@uq.edu.au.; School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, QLD, Australia. c.layton@uq.edu.au.
Jazyk: angličtina
Zdroj: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy [BioDrugs] 2024 Jan; Vol. 38 (1), pp. 73-93. Date of Electronic Publication: 2023 Oct 25.
DOI: 10.1007/s40259-023-00629-y
Abstrakt: Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.
(© 2023. The Author(s).)
Databáze: MEDLINE
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