Isis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, CA, 92010, USA,
J Cardiovasc Transl Res. 2013 Dec;6(6):969-80. doi: 10.1007/s12265-013-9495-7. Epub 2013 Jul 16.
Antisense oligonucleotides and small interfering RNAs, which suppress the translation of specific mRNA target proteins, are emerging as important therapeutic modalities for the treatment of cardiovascular disease. Over the last 25 years, the advances in all aspects of antisense technology, as well as a detailed understanding of the mechanism of action of antisense drugs, have enabled their use as therapeutic agents. These advancements culminated in the FDA approval of the first chronically administered cardiovascular antisense therapeutic, mipomersen, which targets hepatic apolipoprotein B mRNA. This review provides a brief history of antisense technology, highlights the progression of mipomersen from preclinical studies to multiple Phase III registration trials, and gives an update on the status of other cardiovascular antisense therapeutics currently in the clinic.
反义寡核苷酸和小干扰 RNA 可以抑制特定的 mRNA 靶蛋白的翻译，它们正在成为治疗心血管疾病的重要治疗手段。在过去的 25 年中，反义技术的各个方面的进展，以及对反义药物作用机制的详细了解，使得它们可以作为治疗剂使用。这些进展的最终结果是 FDA 批准了第一种长期给药的心血管反义治疗药物 mipomersen，该药物针对肝载脂蛋白 B mRNA。这篇综述提供了反义技术的简要历史，重点介绍了 mipomersen 从临床前研究到多个 III 期注册试验的进展，并更新了目前在临床应用中的其他心血管反义治疗药物的现状。
