RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model

被引：511
作者：
Harper, SQ
Staber, PD
He, XH
Eliason, SL
Martins, IH
Mao, QW
Yang, L
Kotin, RM
Paulson, HL
Davidson, BL [1 ]
机构：
[1] Univ Iowa, Program Gene Therapy, Dept Internal Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Program Gene Therapy, Dept Neurol, Iowa City, IA 52242 USA
[3] Univ Iowa, Program Gene Therapy, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[4] NHLBI, NIH, Bethesda, MD 20892 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 16期
关键词：
short hairpin RNAs; triplet repeat diseases; gene therapy; nanomedicine;
D O I：
10.1073/pnas.0501507102
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HID. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HID. Our data provide support for the further development of RNAi for HD therapy.
引用
收藏
页码：5820 / 5825
页数：6
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