RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model
SQ Harper, PD Staber, X He… - Proceedings of the …, 2005 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2005•National Acad Sciences
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 …
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 …
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.
National Acad Sciences