Department of Internal Medicine, University of Pavia, Via Golgi 19, Pavia, 27100, Italy.
Molecular Cardiology, IRCCS Istituti Clinici Scientifici Maugeri, Via Maugeri 10, Pavia, 27100, Italy.
Cardiovasc Res. 2024 Nov 25;120(14):1664-1682. doi: 10.1093/cvr/cvae207.
Gene therapy is advancing at an unprecedented pace, and the recent success of clinical trials reinforces optimism and trust among the scientific community. Recently, the cardiac gene therapy pipeline, which had progressed more slowly than in other fields, has begun to advance, overcoming biological and technical challenges, particularly in treating genetic heart pathologies. The primary rationale behind the focus on monogenic cardiac diseases is the well-defined molecular mechanisms driving their phenotypes, directly linked to the pathogenicity of single genetic mutations. This aspect makes these conditions a remarkable example of 'genetically druggable' diseases. Unfortunately, current treatments for these life-threatening disorders are few and often poorly effective, underscoring the need to develop therapies to modulate or correct their molecular substrates. In this review we examine the latest advancements in cardiac gene therapy, discussing the pros and cons of different molecular approaches and delivery vectors, with a focus on their therapeutic application in cardiac inherited diseases. Additionally, we highlight the key factors that may enhance clinical translation, drawing insights from previous trials and the current prospects of cardiac gene therapy.
基因治疗正在以前所未有的速度发展，最近临床试验的成功增强了科学界的乐观和信任。最近，心脏基因治疗领域的进展速度比其他领域慢，开始取得进展，克服了生物学和技术方面的挑战，特别是在治疗遗传性心脏疾病方面。关注单基因心脏疾病的主要理由是推动其表型的明确分子机制，这些机制与单一基因突变的致病性直接相关。这使得这些疾病成为“基因可药物治疗”疾病的一个显著例子。不幸的是，目前对这些危及生命的疾病的治疗方法很少，而且往往效果不佳，这突出表明需要开发治疗方法来调节或纠正其分子底物。在这篇综述中，我们探讨了心脏基因治疗的最新进展，讨论了不同分子方法和递药载体的优缺点，重点介绍了它们在心脏遗传性疾病中的治疗应用。此外，我们还强调了可能增强临床转化的关键因素，从之前的试验和心脏基因治疗的现状中汲取了经验。
