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Therapeutic gene targeting approaches for the treatment of dyslipidemias and atherosclerosis

机译:基因治疗血脂异常和动脉粥样硬化的治疗方法

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PURPOSE OF REVIEW: Despite improved therapies, cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, new therapeutic approaches are still needed. In the gene therapy field, RNA interference (RNAi) and regulation of microRNAs (miRNAs) have gained a lot of attention in addition to traditional overexpression based strategies. Here, recent findings in therapeutic gene silencing and modulation of small RNA expression related to atherogenesis and dyslipidemia are summarized. RECENT FINDINGS: Novel gene therapy approaches for the treatment of hyperlipidemia have been addressed. Antisense oligonucleotide and RNAi-based therapies against apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 have shown already efficacy in preclinical and clinical trials. In addition, several miRNAs dysregulated in atherosclerotic lesions and regulating cholesterol homeostasis have been found, which may represent novel targets for future therapies. SUMMARY: New therapies for lowering lipid levels are now being tested in clinical trials, and both antisense oligonucleotide and RNAi-based therapies have shown promising results in lowering cholesterol levels. However, the modulation of inflammatory component in atherosclerosis by gene therapy and targeting of the effects to plaques are still difficult challenges. ? 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
机译:审查目的:尽管疗法得到了改善,但是心血管疾病是全世界发病率和死亡率的主要原因。因此,仍然需要新的治疗方法。在基因治疗领域,除了传统的基于过表达的策略外,RNA干扰(RNAi)和microRNA(miRNA)调控也引起了很多关注。在此,总结了与动脉粥样硬化和血脂异常有关的治疗性基因沉默和小RNA表达调控的最新发现。最近的发现:解决高脂血症的新型基因治疗方法已经得到解决。针对载脂蛋白B100和前蛋白转化酶枯草杆菌蛋白酶/ kexin型9的反义寡核苷酸和基于RNAi的疗法已经在临床前和临床试验中显示出功效。另外,已经发现了在动脉粥样硬化病变中失调并且调节胆固醇稳态的几种miRNA,这可能代表了未来疗法的新靶标。简介:降低脂质水平的新疗法目前正在临床试验中进行测试,反义寡核苷酸和基于RNAi的疗法均已显示出降低胆固醇水平的有希望的结果。然而,通过基因疗法调节动脉粥样硬化中的炎性成分以及将效应靶向于斑块仍然是困难的挑战。 ? 2013威科集团健康|利平科特·威廉姆斯和威尔金斯。

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