Universal RNAi Triggers for the Specific Inhibition of Mutant Huntingtin, Atrophin-1, Ataxin-3, and Ataxin-7 Expression,Molecular Therapy - Nucleic Acids

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Universal RNAi Triggers for the Specific Inhibition of Mutant Huntingtin, Atrophin-1, Ataxin-3, and Ataxin-7 Expression
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2019-12-18 , DOI: 10.1016/j.omtn.2019.12.012
Anna Kotowska-Zimmer ₁ , Yuliya Ostrovska ₁ , Marta Olejniczak ₂

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The expansion of CAG repeats within the coding region of associated genes is responsible for nine inherited neurodegenerative disorders including Huntington’s disease (HD), spinocerebellar ataxias (SCAs), and dentatorubral-pallidoluysian atrophy (DRPLA). Despite years of research aimed at developing an effective method of treatment, these diseases remain incurable and only their symptoms are controlled. The purpose of this study was to develop effective and allele-selective genetic tools for silencing the expression of mutated genes containing expanded CAG repeats. Here we show that repeat-targeting short hairpin RNAs preferentially reduce the levels of mutant huntingtin, atrophin-1, ataxin-3, and ataxin-7 proteins in patient-derived fibroblasts and may serve as universal allele-selective reagents for polyglutamine (polyQ) diseases.

中文翻译：

用于特异性抑制突变亨廷顿蛋白、Atropin-1、Ataxin-3 和 Ataxin-7 表达的通用 RNAi 触发器

相关基因编码区内 CAG 重复序列的扩展导致九种遗传性神经退行性疾病，包括亨廷顿病 (HD)、脊髓小脑性共济失调 (SCAs) 和齿状核红核-苍白球路易体萎缩 (DRPLA)。尽管多年来的研究旨在开发有效的治疗方法，但这些疾病仍然无法治愈，只能控制其症状。本研究的目的是开发有效的等位基因选择性遗传工具，用于沉默含有扩展 CAG 重复序列的突变基因的表达。在这里，我们证明重复靶向短发夹 RNA 优先降低患者来源的成纤维细胞中突变亨廷顿蛋白、atropin-1、ataxin-3 和 ataxin-7 蛋白的水平，并可作为聚谷氨酰胺 (polyQ) 的通用等位基因选择性试剂疾病。

更新日期：2019-12-18

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