Cardiovascular diseases remain the leading cause of global morbidity and mortality, driven by a complex interplay of inherited and acquired factors that limit the long-term effectiveness of conventional pharmacological, surgical, and device-based therapies. Recent advances in gene therapy have positioned adeno-associated virus (AAV) vectors as a promising platform for addressing the molecular determinants of both inherited and non-inherited cardiac disorders. Owing to their favourable safety profile, low pathogenicity, sustained transgene expression, and broad tissue tropism, AAV vectors have evolved as the most comprehensively evaluated viral delivery system in cardiovascular gene therapy.
Method
This classical review was compiled after a comprehensive literature search of major scientific databases, including PubMed, Scopus, and Web of Science, using keywords related to adeno-associated virus, therapies, inherited and non-inherited cardiac disorders. This review provides a comprehensive synthesis of the biological properties of AAV vectors, with emphasis on serotype-specific cardiac tropism, receptor usage, immunogenicity, and durability of gene expression. We critically assess preclinical and clinical evidence supporting AAV-mediated gene delivery across a spectrum of cardiac conditions, including heart failure, cardiomyopathies, ischemic heart disease, and inherited arrhythmias, highlighting both therapeutic successes and translational limitations.
Conclusions
This review highlights the current delivery strategies, genetic cargoes, and emerging genome-editing approaches, which are discussed in the context of efficacy and safety. Key challenges-such as pre-existing immunity, dose-dependent toxicity, off-target transduction, manufacturing scalability, regulatory constraints, and clinical trial design-are analysed to delineate barriers to widespread clinical adoption. Finally, we outline future directions focused on rational capsid engineering, tissue-specific targeting, improved manufacturing pipelines, and optimized clinical strategies required to advance AAV-based gene therapy toward durable and accessible treatments for cardiac diseases.
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