In Search of Adeno-Associated Virus Vectors With Enhanced Cardiac Tropism for Gene Therapy.

Autor: Sasaki N; The Centre for Heart Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Kok CY; The Centre for Heart Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia; Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Westhaus A; Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Alexander IE; Gene Therapy Research Unit, Children's Medical Research Institute and Sydney Children's Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Discipline of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Lisowski L; Translational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warsaw, Poland., Kizana E; The Centre for Heart Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia; Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia. Electronic address: eddy.kizana@sydney.edu.au.
Jazyk: angličtina
Zdroj: Heart, lung & circulation [Heart Lung Circ] 2023 Jul; Vol. 32 (7), pp. 816-824. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1016/j.hlc.2023.06.704
Abstrakt: Globally, adeno-associated virus (AAV) vectors have been increasingly used for clinical gene therapy trials. In Australia, AAV-based gene therapy is available for hereditary diseases such as retinal dystrophy or spinal muscular atrophy 1 (SMA1). Many preclinical studies have used AAV vectors for gene therapy in models of cardiac disease with outcomes of varying translational potential. However, major barriers to effective and safe therapeutic gene delivery to the human heart remain to be overcome. These include tropism, efficient gene transfer, mitigating off-target gene delivery and avoidance of the host immune response. Developing such an enhanced AAV vector for cardiac gene therapy is of great interest to the field of advanced cardiac therapeutics. In this review, we provide an overview of the approaches currently being employed in the search for cardiac cell-specific AAV capsids, ranging from natural AAVs selected as a result of infection and latency in the heart, to the use of cutting-edge molecular techniques to engineer and select AAVs specific for cardiac cells with the use of high-throughput methods.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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