Gene therapy to terminate tachyarrhythmias

ABSTRACT

Introduction

To date, the treatment option for tachyarrhythmia is classified into drug therapy, catheter ablation, and implantable device therapy. However, the efficacy of the antiarrhythmic drugs is limited. Although the indication of catheter ablation is expanding, several fatal tachyarrhythmias are still refractory to ablation. Implantable cardioverter-defibrillator increases survival, but it is not a curable treatment. Therefore, a novel therapy for tachyarrhythmias refractory to present treatments is desired. Gene therapy is being developed as a promising candidate for this purpose, and basic research and translational research have been accumulated in recent years.

Areas covered

This paper reviews the current state of gene therapy for arrhythmias, including susceptible arrhythmias, the route of administration to the heart, and the type of vector to use. We also discuss the latest progress in the technology of gene delivery and genome editing.

Expert opinion

Gene therapy is one of the most promising technologies for arrhythmia treatment. However, additional technological innovation to achieve safe, localized, homogeneous, and long-lasting gene transfer is required for its clinical application.

KEYWORDS:

• Gene therapy
• arrhythmia
• vector
• gene delivery
• atrial fibrillation
• ventricular tachycardia
• exosome

Article highlights

• There is less evidence for gene therapy in clinical practice for arrhythmias than in other fields, but studies of gene therapy using preclinical models are gradually increasing.

• It is necessary to optimize the type of vector and the route of administration to apply gene therapy to the heart, and at present, intracoronary administration of adeno-associated virus is considered to be safe and effective.

• Many studies have reported the use of gene transfer technology for the treatment of arrhythmia substrates in atrial fibrillation and post-myocardial infarction ventricular tachycardia.

• Recently, treatments using new technologies such as genome editing and gene silencing have been studied, and evidence has been accumulated in animal experiments, especially for hereditary arrhythmias.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.