RNA interference for lipid disorders: is this the future?

IF 4.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in lipidology Pub Date : 2026-06-01 Epub Date: 2026-02-09 DOI:10.1097/MOL.0000000000001033

Miguel Nassif, Renata Turrini Jacob Fazoli, Giuliano Generoso

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Abstract

Purpose of review: Advances in the management of lipid disorders have expanded therapeutic options for hypercholesterolemia and beyond. We review the current advances in RNA interference (RNAi) therapies as small interfering RNA (siRNA) drugs, critically assess their clinical positioning, and explore their potential role in reshaping lipid management over the next years.

Recent findings: RNAi enables targeted, durable suppression of key lipid-regulating proteins at the mRNA level. Inclisiran, the first approved RNAi therapy for hypercholesterolemia, achieves about 50% sustained LDL-c reduction with long-interval maintenance dosing, offering an alternative to monoclonal antibodies. Beyond LDL-c lowering, multiple RNAi drugs are in advanced development targeting lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3, aiming to address residual cardiovascular risk. Early safety and adherence data are encouraging, yet pivotal outcome trials and cost-effectiveness analyses are still pending.

Summary: RNAi is a naturally occurring gene-silencing mechanism that can be harnessed therapeutically through siRNA molecules. In lipidology, siRNA-based therapies represent a disruptive technology with the potential to transform both prevention and treatment of atherosclerotic cardiovascular disease. If ongoing trials confirm cardiovascular benefit and safety, RNAi agents could become foundational in personalized lipid management, moving the field toward long-acting, target-specific, and potentially combination-based regimens. The coming years will determine whether RNAi fulfills its promise as the future standard of care in lipid disorders.

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RNA干扰治疗脂质紊乱：这是未来吗？

综述目的：脂质疾病管理的进展扩大了高胆固醇血症及其他疾病的治疗选择。我们回顾了RNA干扰（RNAi）治疗作为小干扰RNA （siRNA）药物的当前进展，批判性地评估了它们的临床定位，并探讨了它们在未来几年重塑脂质管理方面的潜在作用。最近的发现：RNAi能够在mRNA水平上靶向、持久地抑制关键的脂质调节蛋白。Inclisiran是首个被批准用于高胆固醇血症的RNAi治疗药物，在长间隔维持剂量下可实现约50%的持续LDL-c降低，提供了单克隆抗体的替代方案。除了降低LDL-c，多种靶向脂蛋白(a)、载脂蛋白C-III和血管生成素样蛋白3的RNAi药物正处于后期开发阶段，旨在解决剩余心血管风险。早期的安全性和依从性数据令人鼓舞，但关键的结果试验和成本效益分析仍未完成。摘要：RNAi是一种自然发生的基因沉默机制，可以通过siRNA分子进行治疗。在脂质学领域，基于sirna的疗法代表了一种颠覆性技术，有可能改变动脉粥样硬化性心血管疾病的预防和治疗。如果正在进行的试验证实了心血管的益处和安全性，RNAi药物可能成为个性化脂质管理的基础，将该领域推向长效、靶向性和潜在的基于组合的方案。未来几年将决定RNAi是否能实现其作为血脂紊乱的未来护理标准的承诺。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.