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引用次数: 0
摘要
基因疗法瞄准疾病的分子根源,准备彻底改变心血管医学。本文回顾了基因治疗的发展,强调了其过去的进展和未来的潜力与新兴技术。我们首先评估了基础基因添加和沉默策略,注意到单基因心肌病的临床进展以及多因素心力衰竭的重大挫折,主要是由载体递送的核心挑战驱动的。然后,我们讨论了递送平台的演变,从工程腺相关病毒衣壳到靶向脂质纳米颗粒,旨在提高心脏的特异性和安全性。与此同时,基因编辑革命——从基础的Clustered Regularly Interspaced Short Palindromic Repeats-Cas9系统发展到高保真的碱基和引物编辑器——正在以越来越高的精度直接纠正致病性突变。催化这些治疗平台的是最近单细胞基因组学的爆炸式发展,它提供了前所未有的心脏病理学分辨率,揭示了以前被批量分析所掩盖的新的细胞特异性靶点。我们的结论是,这些支柱——基因组学驱动的发现、精确的基因组编辑和靶向递送——的协同融合正在创造一个精确心脏病学的新范例,将该领域从慢性管理转向持久的、治愈性的干预。
Precision cardiology: Integrating gene therapy, genome editing, and single-cell genomics.
Gene therapy is poised to revolutionize cardiovascular medicine by targeting the molecular roots of disease. This review examines the evolution of gene therapy, highlighting its past progress and future potential with emerging technologies. We first assess foundational gene addition and silencing strategies, noting clinical progress for monogenic cardiomyopathies alongside significant setbacks in multifactorial heart failure, driven mainly by the central challenge of vector delivery. We then discuss the evolution of delivery platforms, from engineered adeno-associated virus capsids to targeted lipid nanoparticles, which are designed to enhance cardiac specificity and safety. Concurrently, the gene editing revolution-progressing from the foundational Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 system to high-fidelity base and prime editors-is enabling the direct correction of pathogenic mutations with increasing precision. Catalyzing these therapeutic platforms is the recent explosion in single-cell genomics, which provides an unprecedented resolution of cardiac pathology, revealing novel cell-specific targets previously obscured by bulk analysis. We conclude that the synergistic convergence of these pillars-genomics-driven discovery, precision genome editing, and targeted delivery-is creating a new paradigm of precision cardiology, moving the field from chronic management towards durable, curative interventions.
期刊介绍:
The official journal of the Japanese College of Cardiology is an international, English language, peer-reviewed journal publishing the latest findings in cardiovascular medicine. Journal of Cardiology (JC) aims to publish the highest-quality material covering original basic and clinical research on all aspects of cardiovascular disease. Topics covered include ischemic heart disease, cardiomyopathy, valvular heart disease, vascular disease, hypertension, arrhythmia, congenital heart disease, pharmacological and non-pharmacological treatment, new diagnostic techniques, and cardiovascular imaging. JC also publishes a selection of review articles, clinical trials, short communications, and important messages and letters to the editor.