Gene and Cell Therapy for Cardiac Arrhythmias

Abstract

Purpose: In the last decade, interest in gene therapy as a therapeutic technology has increased, largely driven by an exciting yet modest number of successful applications for monogenic diseases. Setbacks in the use of gene therapy for cardiac disease have motivated efforts to develop vectors with enhanced tropism for the heart and more efficient delivery methods. Although monogenic diseases are the logical target, cardiac arrhythmias represent a group of conditions amenable to gene therapy because of focal targets (biological pacemakers, nodal conduction, or stem cell-related arrhythmias) or bystander effects on cells not directly transduced because of electrical coupling.

Methods: This review provides a contemporary narrative of the field of gene therapy for experimental cardiac arrhythmias, including those associated with stem cell transplant. Recent articles published in the English language and available through the PubMed database and other prominent literature are discussed.

Findings: The promise of gene therapy has been realized for a handful of monogenic diseases and is actively being pursued for cardiac applications in preclinical models. With improved vectors, it is likely that cardiac disease will also benefit from this technology. Cardiac arrhythmias, whether inherited or acquired, are a group of conditions with a potentially lower threshold for phenotypic correction and as such hold unique potential as targets for cardiac gene therapy.

Implications: There has been a proliferation of research on the potential of gene therapy for cardiac arrhythmias. This body of investigation forms a strong basis on which further developments, particularly with viral vectors, are likely to help this technology progress along its translational trajectory.

Keywords: Adeno-associated virus; Arrhythmia; Biological pacemaker; Gene therapy; Ventricular arrhythmia.