Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia
Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia
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DOI：
10.1080/14740338.2022.1988568
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发表时间：
2021-10-15
影响因子：
3.1
通讯作者：
Rizzo, Manfredi
中科院分区：
文献类型：
--
作者：
Banerjee, Yajnavalka;Pantea Stoian, Anca;Rizzo, Manfredi
Inclisiran是一种新型转录后基因沉默疗法，通过RNA干扰抑制前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）的合成，具有强效、剂量依赖性、持久的降低LDL-C的作用，因此是治疗血脂异常、降低急性心血管（CV）事件风险的有效药物。它是安全且耐受性良好的。涵盖领域本文旨在回顾inclisiran的作用机制，同时根据ORION计划的临床试验数据评估其治疗血脂异常的有效性和安全性。专家意见 ORION 项目的临床试验数据证明了 inclisiran 对血脂异常患者的有效性和安全性。临床试验中，inclisiran 组和安慰剂组的不良事件相似，但 inclisiran 组的注射部位反应比安慰剂组更常见。尽管与其他 PCSK9 靶向治疗策略相比，功效和安全性的结合使 inclisiran 成为治疗血脂异常的良好选择，然而，进一步的研究应排除 inclisiran 通过较低亲和力相互作用可能影响生理环境中其他 mRNA 的可能性。
Introduction Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. Areas covered This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. Expert opinion Data from the clinical trials in the ORION program demonstrated efficacy and safety of inclisiran in patients with dyslipidemia. Adverse events were similar in the inclisiran and placebo groups in the clinical trials, although injection-site reactions were more frequent with inclisiran than with placebo. Although the combination of efficacy and safety makes inclisiran a good option for the treatment of dyslipidemia compared to other PCSK9 targeting therapeutic strategies, however, further studies should exclude the possibility that inclisiran, through lower-affinity interactions, may influence other mRNAs in the physiological milieu.