Gene Therapies in Atrial Fibrillation

J Cardiovasc Transl Res. 2025 Dec;18(6):1503-1510. doi: 10.1007/s12265-025-10685-0. Epub 2025 Oct 14.

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, yet current therapies-including drugs and catheter ablation-remain suboptimal. Gene therapy offers a promising way to modulate AF's molecular drivers. This review summarizes recent preclinical studies using viral and non-viral vectors, atrial-specific delivery strategies, and key targets such as ion channels, fibrosis, and oxidative stress. Despite promising results, no AF gene therapy has FDA approval, due to challenges in atrial targeting, immune control, and durable expression. Closing this translational gap is critical for future AF gene therapy.

Keywords: Atrial fibrillation; Electrical remodeling; Gene therapy; Oxidative stress; Structural remodeling.

Publication types

  • Review

MeSH terms

  • Action Potentials
  • Animals
  • Atrial Fibrillation* / genetics
  • Atrial Fibrillation* / metabolism
  • Atrial Fibrillation* / physiopathology
  • Atrial Fibrillation* / therapy
  • Gene Transfer Techniques
  • Genetic Therapy* / adverse effects
  • Genetic Therapy* / methods
  • Genetic Vectors
  • Heart Rate* / genetics
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Oxidative Stress
  • Treatment Outcome

Substances

  • Ion Channels