Vascular diseases such as atherosclerosis, aneurysms, and peripheral arterial disease remain leading causes of morbidity and mortality, with current treatments primarily managing symptoms rather than addressing underlying molecular drivers. Gene therapy offers a promising avenue for targeted intervention, and recent advances in multi-omics approaches-including genomics, transcriptomics, and epigenetics-are enhancing the precision and efficacy of these therapies. High-throughput sequencing and integrative omics analyses have facilitated the identification of causal genes, non-coding RNAs, and epigenetic regulators involved in vascular pathology. This review examines how multi-omics frameworks inform gene therapy design, from genomic editing of cardiovascular disease loci to transcriptome-guided RNA therapies and epigenetic modulation of disease states. We highlight emerging applications such as CRISPR-based interventions, RNA therapeutics, and individualized precision medicine strategies. Additionally, we address analytical challenges, implementation hurdles, and ethical considerations in translating multi-omics-driven gene therapies into clinical practice. By integrating systems biology and advanced computational methods, the convergence of multi-omics and gene therapy holds transformative potential for vascular medicine, offering new avenues for disease modification and patient-specific therapeutic solutions.
Dong et al. (Tue,) studied this question.