Sequence-dependent and independent inhibition specific for mutant ataxin-3 by small interfering RNA

被引：28

作者：

Li, Y

Yokota, T

Matsumura, R

Taira, K

Mizusawa, H

机构：

[1] Tokyo Med & Dent Univ, Grad Sch, Dept Neurol & Neurol Sci, Tokyo, Japan

[2] Nara Med Univ, Dept Neurol, Nara, Japan

[3] Univ Tokyo, Sch Engn, Dept Chem & Biotechnol, Tokyo, Japan

来源：

ANNALS OF NEUROLOGY | 2004年 / 56卷 / 01期

关键词：

D O I：

10.1002/ana.20141

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In Machado-Joseph disease (MJD) gene, there is a C/G polymorphism immediately after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C, whereas about half of wild-type alleles are followed by G. Using this C/G polymorphism, we have engineered the small interfering RNA (siRNA) which decreased the expression of mutant ataxin-3, Q79C, by 96.0%, whereas there was minimal reduction on that of the wild type, Q22G (5.9%). Furthermore, unexpectedly, the expression of another wild-type allele, Q22c, was also much less suppressed (22.5%) by this siRNA possibly due to difference of the secondary structure of the target RNA. This is the first report of sequence-independent discrimination of mutant and wild-type alleles by siRNA.

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页码：124 / 129

页数：6

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