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.

中文翻译：

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心脏病的基因治疗：方法、挑战和未来方向


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，与其他领域相比进展缓慢的心脏基因治疗管道已经开始前进，克服了生物学和技术挑战，特别是在治疗遗传性心脏病方面。关注单基因心脏病背后的主要原理是驱动其表型的明确分子机制，与单基因突变的致病性直接相关。这使得这些疾病成为“基因药物”疾病的显着例子。不幸的是，目前针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，这凸显了开发调节或纠正其分子底物的疗法的必要性。在这篇综述中，我们研究了心脏基因治疗的最新进展，讨论了不同分子方法和递送载体的优缺点，重点关注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当前前景中汲取见解。