Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques. Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen (AGT) are produced. Current targets in lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), apolipoprotein C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production. This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.

中文翻译：

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核酸靶向治疗预防心血管疾病的进展


基于核酸的疗法正在迅速开发，用于预防和管理心血管疾病（CVD）。过去十年中，这些疗法在递送、安全性和有效性方面取得了显着进步。这些疗法还可以调节传统药物或抗体无法充分解决的治疗靶点。正在开发的用于预防 CVD 的核酸靶向疗法包括 RNA 靶向方法，包括反义寡核苷酸 (ASO)、小干扰 RNA (siRNA) 和新型基因组编辑技术。遗传学研究已经确定了潜在的治疗靶点，这些靶点被认为在 CVD 的发生和进展中发挥着致病作用。 RNA 和 DNA 靶向治疗药物可以特别好地输送到肝脏，肝脏是产生致动脉粥样硬化脂蛋白和血管紧张素原 (AGT) 的地方。目前脂质代谢的靶标包括前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9)、载脂蛋白 A (ApoA)、载脂蛋白 C3 (ApoC3)、血管生成素样 3 (ANGPTL3)。心血管预防中核酸靶向疗法的几个大规模临床开发项目正在进行中，考虑到这些疗法的长期作用，从治疗依从性的角度来看，这也可能具有吸引力。除了基因组编辑之外，基因转移的概念目前正在临床前和临床研究中进行评估，作为解决低密度脂蛋白受体缺陷的潜在方法。此外，正在进行的研究正在探索使用 RNA 靶向疗法通过减少肝脏血管紧张素原 (AGT) 的产生来治疗动脉高血压。 本综述总结了 siRNA 和 ASO 疗法以及基因编辑快速转化为治疗血脂异常和动脉高血压以预防 CVD 的临床研究。它还概述了可能与心血管医学的未来相关的潜在创新治疗方案。