Bains Sahej, Giudicessi John R, Odening Katja E, Ackerman Michael J
Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN, USA.
Nat Rev Cardiol. 2025 May 23. doi: 10.1038/s41569-025-01168-5.
Cardiovascular diseases are the leading cause of death globally, with cardiac arrhythmias contributing substantially to this burden. Gene therapy, which directly targets the underlying disease pathobiology, offers an appealing treatment strategy for cardiac arrhythmias owing to its potential as a one-time, curative solution. Over the past two decades, substantial efforts have been made to develop new gene therapy approaches that overcome the limitations of conventional treatments. In this Review, we describe the rationale for gene therapy to treat cardiac arrhythmias; discuss advantages and disadvantages of gene silencing, gene replacement, gene suppression-and-replacement and gene editing technologies; summarize vector modalities and delivery approaches used in the field; present examples of gene therapy strategies used for atrial and ventricular arrhythmias; and highlight the current challenges and limitations in the gene therapy field.
心血管疾病是全球主要的死亡原因,心律失常在这一负担中占很大比例。基因疗法直接针对潜在的疾病病理生物学,因其有可能成为一次性的治愈性解决方案,为心律失常提供了一种有吸引力的治疗策略。在过去二十年中,人们付出了巨大努力来开发新的基因疗法,以克服传统治疗方法的局限性。在本综述中,我们阐述了基因疗法治疗心律失常的基本原理;讨论基因沉默、基因替代、基因抑制与替代以及基因编辑技术的优缺点;总结该领域使用的载体形式和递送方法;列举用于心房和心室心律失常的基因疗法策略实例;并强调基因疗法领域当前面临的挑战和局限性。