Gene therapy strategies for cardiac electrical dysfunction

Cardiac disease is frequently associated with abnormalities in electrical function that can severely impair cardiac performance with potentially fatal consequences. The available therapeutic options have some efficacy but are far from perfect. The curative potential of gene therapy makes it an attractive approach for the treatment of cardiac arrhythmias. To date, gene therapy research strategies have targeted three major classes of cardiac arrhythmias: (1) ventricular arrhythmias, (2) atrial fibrillation, and (3) bradyarrhythmias. Various vehicles for gene transfer have been employed with adeno-associated viral gene delivery being the preferred choice for long-term gene expression and adenoviral gene delivery for short-term proof-of-concept work. In combination with the development of novel delivery methods, gene therapy may prove to be an effective strategy to eliminate the most debilitating of arrhythmias. This article is part of a Special Section entitled “Special Section: Cardiovascular Gene Therapy”.

Research highlights:Atrial gene transfer of KCNH2-G628S gene transfer delays the onset of atrial fibrillation.Atrioventricular nodal gene transfer of GNAI2 reduces ventricular rate in atrial fibrillation.KCNH2-G628S or SCN4A gene transfer reduces or eliminates ventricular arrhythmias after infarction.ATP2A2 gene transfer reduces cardiac repolarization alternans.Focal HCN1-4 gene transfer creates nodes of automaticity.