Selective silencing of a mutant transthyretin allele by small interfering RNAs
Selective silencing of a mutant transthyretin allele by small interfering RNAs
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DOI：
10.1016/j.bbrc.2005.09.142
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发表时间：
2005-11-25
影响因子：
3.1
通讯作者：
Onodera, O
中科院分区：
文献类型：
--
作者：
Kurosawa, T;Igarashi, S;Onodera, O
家族性淀粉样多发性神经病（FAP）是一种遗传性系统性淀粉样变性，由编码甲状腺素运载蛋白（TTR）的基因的显性作用错义突变引起。最常见的突变TTR是Va130Met型，由点突变引起。由于淀粉样蛋白原纤维的主要成分是突变TTR，选择性抑制突变TTR表达的药物可能是强大的治疗工具。本研究旨在评估小干扰RNA（siRNA）在细胞培养系统中选择性沉默突变型Va130Met TTR的用途。我们已经鉴定了一种siRNA，其特异性抑制突变体而非野生型TTR表达，即使在表达两种等位基因的细胞中。因此，这种基于siRNA的方法可能具有用于FAR（c）2005 Elsevier Inc.的基因治疗的潜力。All rights reserved.
Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic amyloidosis caused by dominantly acting missense mutations in the gene encoding transthyretin (TTR). The most common mutant TTR is of the Va130Met type, which results from a point mutation. Because the major constituent of amyloid fibrils is mutant TTR, agents that selectively suppress mutant TTR expression could be powerful therapeutic tools. This study has been performed to evaluate the use of small interfering RNAs (siRNAs) for the selective silencing of mutant Va130Met TTR in cell culture systems. We have identified an siRNA that specifically inhibits mutant, but not wild-type, TTR expression even in cells expressing both alleles. Thus, this siRNA-based approach may have potential for the gene therapy of FAR (c) 2005 Elsevier Inc. All rights reserved.