Perspective of Viral Genetherapy in Cardiovascular Diseases

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide and are often inadequately managed by standard pharmacologic or surgical treatments. As a result, viral gene therapy has emerged as a promising strategy to address the molecular roots of CVD by enabling gene delivery, correction, or modulation directly within cardiac and vascular tissues. In this approach, therapeutic genes are introduced using viral vectors such as adeno-associated virus (AAV), adenovirus, and lentivirus. These vectors can be engineered to target specific cell types—including cardiomyocytes, endothelial cells, and smooth muscle cells—with high precision. Such targeting allows for potential treatment of conditions like heart failure, myocardial infarction, arrhythmias, and atherosclerosis. Preclinical and clinical studies have demonstrated that viral gene therapy can enhance cardiac contractility, promote vascular regeneration, and reverse maladaptive structural remodeling of the heart and vessels. Several clinical trials have attracted global attention, particularly those aiming to restore SERCA2a function in chronic heart failure and to use VEGF for ischemic angiogenesis. These trials showed acceptable safety profiles and modest therapeutic benefits. However, issues such as vector immunogenicity, suboptimal delivery efficiency, limited tissue specificity, restricted packaging capacity, and challenges in sustaining long-term transgene expression have so far prevented widespread clinical adoption. This article offers an in-depth review of the mechanisms underlying viral gene therapy, the characteristics of different viral vectors, key outcomes from clinical trials, strategies for targeted delivery, and emerging innovations in the field. As gene editing technologies and vector engineering continue to advance, viral gene therapy is poised to become a cornerstone of precision cardiology and regenerative cardiovascular medicine.