治疗性基因靶向方法治疗血脂异常和动脉粥样硬化。
Therapeutic gene targeting approaches for the treatment of dyslipidemias and atherosclerosis.
机构信息
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland.
出版信息
Curr Opin Lipidol. 2013 Apr;24(2):116-22. doi: 10.1097/MOL.0b013e32835da13c.
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.
目的综述
尽管治疗方法有所改善,但心血管疾病仍是全球发病率和死亡率的主要原因。因此,仍需要新的治疗方法。在基因治疗领域,除了传统的过表达策略外,RNA 干扰 (RNAi) 和 microRNAs (miRNAs) 的调控也引起了广泛关注。本文总结了与动脉粥样硬化和血脂异常相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
针对高脂血症的新型基因治疗方法已被提出。针对载脂蛋白 B100 和脯氨酸羧肽酶/枯草杆菌蛋白酶 kexin 9 的反义寡核苷酸和 RNAi 疗法已在临床前和临床试验中显示出疗效。此外,还发现了几种在动脉粥样硬化病变中失调并调节胆固醇稳态的 miRNA,它们可能成为未来治疗的新靶点。
总结
目前正在临床试验中测试降低血脂水平的新疗法,反义寡核苷酸和 RNAi 疗法在降低胆固醇水平方面均显示出良好的效果。然而,基因治疗对动脉粥样硬化炎症成分的调节以及针对斑块的靶向治疗仍然是具有挑战性的难题。