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

Scott Q. Harper, Patrick D. Staber, Xiaohua He, Steven L. Eliason, Inês H. Martins, Qinwen Mao, Linda Yang, Robert M. Kotin, Henry L. Paulson, Beverly L. Davidson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

523 Scopus citations

Abstract

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 HD. 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 HD. Our data provide support for the further development of RNAi for HD therapy.

Original languageEnglish (US)
Pages (from-to)5820-5825
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number16
DOIs
StatePublished - Apr 19 2005

Keywords

  • Gene therapy
  • Nanomedicine
  • Short hairpin RNAs
  • Triplet repeat diseases

ASJC Scopus subject areas

  • General

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