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基因治疗心房颤动。

Gene therapy for atrial fibrillation.

机构信息

From the Division of Cardiology, University of Massachusetts Medical School, Worcester, MA, United States of America.

From the Division of Cardiology, University of Massachusetts Medical School, Worcester, MA, United States of America.

出版信息

J Mol Cell Cardiol. 2024 Nov;196:84-93. doi: 10.1016/j.yjmcc.2024.09.004. Epub 2024 Sep 11.

DOI:10.1016/j.yjmcc.2024.09.004
PMID:39270930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11534567/
Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Current limitations of pharmacological and ablative therapies motivate the development of novel therapies as next generation treatments for AF. The arrhythmia mechanisms creating and sustaining AF are key elements in the development of this novel treatment. Gene therapy provides a useful platform that allows us to regulate the mechanisms of interest using a suitable transgene(s), vector, and delivery method. Effective gene therapy strategies in the literature have targeted maladaptive electrical or structural remodeling that increase vulnerability to AF. In this review, we will summarize key elements of gene therapy for AF, including molecular targets, gene transfer vectors, atrial gene delivery and preclinical efficacy and toxicity testing. Recent advances and challenges in the field will be also discussed.

摘要

心房颤动(AF)是成年人中最常见的持续性心律失常。目前药物和消融治疗的局限性促使人们开发新的治疗方法,作为 AF 的下一代治疗方法。导致和维持 AF 的心律失常机制是开发这种新型治疗方法的关键要素。基因治疗提供了一个有用的平台,使我们能够使用合适的转基因(s)、载体和递送方法来调节感兴趣的机制。文献中有效的基因治疗策略针对的是适应性不良的电或结构重构,这些重构增加了对 AF 的易感性。在这篇综述中,我们将总结 AF 基因治疗的关键要素,包括分子靶点、基因转移载体、心房基因递送以及临床前疗效和毒性测试。还将讨论该领域的最新进展和挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b01/11534567/092206bf37ee/nihms-2023040-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b01/11534567/092206bf37ee/nihms-2023040-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b01/11534567/092206bf37ee/nihms-2023040-f0002.jpg

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本文引用的文献

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Does the small conductance Ca-activated K current I flow under physiological conditions in rabbit and human atrial isolated cardiomyocytes?在生理条件下,兔和人心房分离心肌细胞中是否存在小电导钙激活钾电流 I 流?
J Mol Cell Cardiol. 2023 Oct;183:70-80. doi: 10.1016/j.yjmcc.2023.09.002. Epub 2023 Sep 12.
2
Preclinical safety and biodistribution assessment of Ad-KCNH2-G628S administered via atrial painting in New Zealand white rabbits.经心房涂抹给予 Ad-KCNH2-G628S 的新西兰白兔的临床前安全性和生物分布评估。
Basic Clin Pharmacol Toxicol. 2023 Aug;133(2):179-193. doi: 10.1111/bcpt.13885. Epub 2023 May 23.
3
GJA1-20k Rescues Cx43 Localization and Arrhythmias in Arrhythmogenic Cardiomyopathy.
GJA1-20k挽救致心律失常性心肌病中的Cx43定位及心律失常。
Circ Res. 2023 Mar 17;132(6):744-746. doi: 10.1161/CIRCRESAHA.122.322294. Epub 2023 Feb 22.
4
Differential Sodium Current Remodelling Identifies Distinct Cellular Proarrhythmic Mechanisms in Paroxysmal vs Persistent Atrial Fibrillation.钠电流差异重塑揭示阵发性与持续性心房颤动不同的细胞促心律失常机制
Can J Cardiol. 2023 Mar;39(3):277-288. doi: 10.1016/j.cjca.2022.12.023. Epub 2022 Dec 28.
5
Organelle-targeted therapies: a comprehensive review on system design for enabling precision oncology.细胞器靶向治疗:实现精准肿瘤学的系统设计全面综述。
Signal Transduct Target Ther. 2022 Nov 19;7(1):379. doi: 10.1038/s41392-022-01243-0.
6
Inflammatory signalling in atrial cardiomyocytes: a novel unifying principle in atrial fibrillation pathophysiology.心房肌细胞中的炎症信号转导:心房颤动病理生理学中的一个新的统一原则。
Nat Rev Cardiol. 2023 Mar;20(3):145-167. doi: 10.1038/s41569-022-00759-w. Epub 2022 Sep 15.
7
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