Allele-Selective Inhibition of Mutant Huntingtin by Peptide Nucleic Acid-Peptide Conjugates, Locked Nucleic Acid, and Small Interfering RNA
Allele-Selective Inhibition of Mutant Huntingtin by Peptide Nucleic Acid-Peptide Conjugates, Locked Nucleic Acid, and Small Interfering RNA
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DOI：
10.1111/j.1749-6632.2009.04975.x
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Corey, David R.
中科院分区：
文献类型：
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作者：
Hu, Jiaxin;Matsui, Masayuki;Corey, David R.
抑制突变等位基因的表达同时保持野生型蛋白的表达的能力可能为治疗亨廷顿病(HD)和其他遗传病理提供了一种有用的方法。亨廷顿蛋白的突变形式(HTT)是导致HD的蛋白质，由包含一个扩展的CAG重复序列的mRNA编码。我们证明了与CAG重复序列互补的肽核酸和锁定的核酸选择性地阻断了突变的HTT的表达。抑制的选择性至少与针对缺失多态的小干扰RNA所显示的一样好。我们的数据表明，反义低聚物作为一种抗HD治疗策略是很有前途的研究对象。
The ability to inhibit expression of a mutant allele while retaining expression of a wildtype protein might provide a useful approach to treating Huntington's Disease (HD) and other inherited pathologies. The mutant form of huntingtin (HTT), the protein responsible for HD, is encoded by an mRNA containing an expanded CAG repeat. We demonstrate that peptide nucleic acid conjugates and locked nucleic acids complementary to the CAG repeat selectively block expression of mutant HTT. The selectivity of inhibition is at least as good as that shown by a small interfering RNA targeted to a deletion polymorphism. Our data suggest that antisense oligomers are promising subjects for further development as an anti-HD therapeutic strategy.