Precision cardiology: Integrating gene therapy, genome editing, and single-cell genomics

Gene therapy is poised to revolutionize cardiovascular medicine by targeting the molecular roots of disease. This review examines the evolution of gene therapy, highlighting its past progress and future potential with emerging technologies. We first assess foundational gene addition and silencing strategies, noting clinical progress for monogenic cardiomyopathies alongside significant setbacks in multifactorial heart failure, driven mainly by the central challenge of vector delivery. We then discuss the evolution of delivery platforms, from engineered adeno-associated virus capsids to targeted lipid nanoparticles, which are designed to enhance cardiac specificity and safety. Concurrently, the gene editing revolution-progressing from the foundational Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 system to high-fidelity base and prime editors-is enabling the direct correction of pathogenic mutations with increasing precision. Catalyzing these therapeutic platforms is the recent explosion in single-cell genomics, which provides an unprecedented resolution of cardiac pathology, revealing novel cell-specific targets previously obscured by bulk analysis. We conclude that the synergistic convergence of these pillars-genomics-driven discovery, precision genome editing, and targeted delivery-is creating a new paradigm of precision cardiology, moving the field from chronic management towards durable, curative interventions.