Advancing gene and base editing for cardiovascular disease: overcoming barriers in delivery, precision and safety

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality despite major advances in pharmacological, devices, and surgical care. Gene editing technologies have introduced a transformative approach to correct pathogenic variants and modulate disease pathways. This review highlights recent progress in editing technologies that are currently or may soon be applied to address cardiovascular disorders, summarizes recent preclinical and clinical studies that demonstrate improved precision and efficacy, and examines technical and translational challenges that must be overcome for broader clinical application.

We summarize preclinical advances, including refined target selection, improved delivery strategies, and enhanced therapeutic efficiency. We highlight emerging technologies that aim to overcome longstanding constraints such as limited vector cargo capacity, protospacer-adjacent motif (PAM) incompatibility, chromatin accessibility, suboptimal editing efficiency, and off-target activity. We also summarize the increasing clinical experience with in-vivo editing - particularly using lipid nanoparticle (LNP) and adeno-associated virus (AAV)-based platforms - that has also revealed important safety considerations, including vector immunogenicity, systemic inflammation, and organ-specific toxicities.

Despite rapid progress, successful clinical translation of gene and base editing for CVD continues to hinge on two central challenges: efficient and precise delivery and mitigation of immunogenicity and toxicity from both delivery vectors and gene-editing enzymes. Although next-generation editors and targeted delivery systems have expanded the scope of feasible cardiovascular applications, overcoming these biological barriers remains the critical step toward achieving well tolerated, durable, one-time genomic therapies. Continued innovation in vector engineering, tissue-selective delivery, and immunologic risk mitigation will be essential for advancing editing technologies into cardiovascular care.