[RNAi versus Huntington's disease]
>>Published online before print April 5, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0501507102
Medical Sciences
RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model
( short hairpin RNAs | triplet repeat diseases | gene therapy | nanomedicine )
Scott Q. Harper *, Patrick D. Staber *, Xiaohua He *, Steven L. Eliason *, Inês H. Martins *, Qinwen Mao *, Linda Yang , Robert M. Kotin , Henry L. Paulson *, and Beverly L. Davidson *¶||
*Program in Gene Therapy, Departments of Internal Medicine, Neurology, and ¶Physiology and Biophysics, University of Iowa, Iowa City, IA 52242; and National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
Communicated by Michael J. Welsh, University of Iowa College of Medicine, Iowa City, IA, March 2, 2005 (received for review January 12, 2005)
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.<<
Beverly Davidson has published some landmark stuff in RNAi.
Regarding NSTK, it's weird that ALNY got huge play from demonstrating systemic delivery, and NSTK is getting no respect from the market today. I'm not sure why.
Cheers, Tuck |
