The Fomivirsen, Patisiran, and Givosiran Odyssey: How the Success Stories May Pave the Way for Future Clinical Translation of Nucleic Acid Drugs.

IF 5.4 2区医学 Q1 IMMUNOLOGY

BioDrugs Pub Date : 2025-04-05 DOI:10.1007/s40259-025-00711-7

Mona Mansouri, Kimia Mansouri, Zahra Taheri, Samira Hossaini Alhashemi, Ali Dehshahri

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引用次数: 0

Abstract

Over the past 25 years, the approval of several nucleic acid-based drugs by the US Food and Drug Administration (FDA) has marked a significant milestone, establishing nucleic acid drugs as a viable therapeutic modality. These groundbreaking discoveries are the result of some crucial points in the timeline of nucleic acid drug development. The inventions used in fomivirsen (Vitravene; Isis Pharmaceuticals) development paved the road for structural backbone modifications as well as nucleobase and sugar modifications. The approval of patisiran (Onpattro; Alnylam) demonstrated an effective and safe delivery system for small interfering RNA (siRNA), extending potential applications to other nucleic acids such as messenger RNA (mRNA). Givosiran (Givlaari; Alnylam) further revolutionized the field with a carrier-free, targeted platform, utilizing N-Acetylgalactosamine (GalNAc)-siRNA conjugates to enable efficient delivery, expanding therapeutic applications beyond rare genetic disorders to more common conditions such as hyperlipidemia and hypertension. In this review paper, we highlight the evolution of nucleic acid-based drug development, focusing on the pioneering agents fomivirsen, patisiran, and givosiran, and discuss the ongoing challenges in advancing these therapeutics and vaccines.

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Fomivirsen， Patisiran和Givosiran奥德赛：成功的故事如何为未来核酸药物的临床转化铺平道路。

在过去的25年里，美国食品和药物管理局（FDA）批准了几种基于核酸的药物，这是一个重要的里程碑，标志着核酸药物成为一种可行的治疗方式。这些突破性的发现是核酸药物开发时间表上一些关键点的结果。这些发明被用在formivirsen (Vitravene；Isis制药公司的发展为结构主链修饰以及核碱基和糖修饰铺平了道路。patisiran （Onpattro）的批准；Alnylam)证明了一种有效和安全的小干扰RNA （siRNA）递送系统，将潜在的应用扩展到其他核酸如信使RNA （mRNA）。Givosiran (Givlaari;Alnylam)进一步革新了该领域的无载体靶向平台，利用n -乙酰半乳糖胺(GalNAc)-siRNA偶联物实现高效递送，将治疗应用从罕见的遗传疾病扩展到更常见的疾病，如高脂血症和高血压。在这篇综述文章中，我们重点介绍了基于核酸的药物开发的发展，重点介绍了fomivirsen， patisiran和givosiran的先驱药物，并讨论了推进这些治疗方法和疫苗的持续挑战。

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

BioDrugs 医学-免疫学

CiteScore

12.60

自引率

2.90%

发文量

审稿时长

>12 weeks

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