三核苷酸重复基因的等位基因选择性抑制。
Allele-selective inhibition of trinucleotide repeat genes.
机构信息
Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
出版信息
Drug Discov Today. 2012 May;17(9-10):443-50. doi: 10.1016/j.drudis.2012.01.006. Epub 2012 Jan 18.
Abstract
Expanded trinucleotide repeats cause Huntington's disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develop strategies to lower levels of mutant protein while leaving adequate wild-type protein levels. Here, we review approaches that use synthetic nucleic acids to inhibit expression of trinucleotide repeat genes.
摘要
扩展的三核苷酸重复导致亨廷顿病 (HD) 和许多其他神经退行性疾病。目前尚无针对这些破坏性疾病的治疗方法，迫切需要新的治疗方法。每种三核苷酸重复疾病都是由一个基因的突变引起的，而阻断突变基因表达的药物为治疗提供了一个有前景的选择。阻断突变和野生型等位基因表达的治疗方法可能会产生不良反应，这给研究人员带来了挑战，需要开发降低突变蛋白水平而不影响野生型蛋白水平的策略。在这里，我们综述了使用合成核酸抑制三核苷酸重复基因表达的方法。
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