Year: 2024
Type: article
Abstract: Adeno-associated viral (AAV) vectors have emerged as crucial tools in advancing gene therapy for skeletal diseases, offering the potential for sustained expression with low postinfection immunogenicity and pathogenicity. Preclinical studies support both the therapeutic efficacy and safety of these vectors, illustrating the promise of AAV-mediated gene therapy. Emerging technologies and innovations in AAV-mediated gene therapy strategies, such as gene addition, gene replacement, gene silencing, and gene editing, offer new approaches to clinical application. Recently, the increasing preclinical applications of AAV to rare skeletal diseases, such as fibrodysplasia ossificans progressiva (FOP) and osteogenesis imperfecta (OI), and prevalent bone diseases, such as osteoporosis, bone fracture, critical-sized bone defects, and osteoarthritis, have been reported. Despite existing limitations in clinical use, such as high cost and safety, the AAV-mediated gene transfer platform is a promising approach to deliver therapeutic gene(s) to the skeleton to treat skeletal disorders, including those otherwise intractable by other therapeutic approaches. This review provides a comprehensive overview of the therapeutic advancements, challenges, limitations, and solutions within AAV-based gene therapy for prevalent and rare skeletal diseases.
Source: Human Gene Therapy
DOI: 10.1089/hum.2024.022
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Wellcome Trust, International Fibrodysplasia Ossificans Progressiva Association, Pershing Square Sohn Cancer Research Alliance, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G181471636, Novel approach to promote bone formation in osteoporosis using bone-homing mesenchymal stem cells, G2987695138, G378594451, G4166271608, Identification of novel regulators governing osteoclast-osteoblast coupling, G4558027284, Next Generation of Recombinant AAV Serotype For Gene Therapy, G5641026441, Develop combinatorial non-viral and viral CRISPR delivery for lung diseases, An AAV-mediated functional cure and its impact on the reservoir, G8598155764, Oligodendrocyte-focused rAAV gene therapy strategies for Canavan disease and Leukodystrophies
OpenAlex ID: W4393223047