Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/12776
Title: Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease
Authors: Alves, Sandro 
Nascimento-Ferreira, Isabel 
Auregan, Gwennaëlle 
Hassig, Raymonde 
Dufour, Noëlle 
Brouillet, Emmanuel 
Lima, Maria C. Pedroso de 
Hantraye, Philippe 
Almeida, Luís Pereira de 
Déglon, Nicole 
Issue Date: Oct-2008
Publisher: Public Library of Science
Citation: PloS One. 3:10 (2008) e3341
Abstract: Recent studies have demonstrated that RNAi is a promising approach for treating autosomal dominant disorders. However, discrimination between wild-type and mutant transcripts is essential, to preserve wild-type expression and function. A single nucleotide polymorphism (SNP) is present in more than 70% of patients with Machado-Joseph disease (MJD). We investigated whether this SNP could be used to inactivate mutant ataxin-3 selectively. Lentiviral-mediated silencing of mutant human ataxin-3 was demonstrated in vitro and in a rat model of MJD in vivo. The allele-specific silencing of ataxin-3 significantly decreased the severity of the neuropathological abnormalities associated with MJD. These data demonstrate that RNAi has potential for use in MJD treatment and constitute the first proof-of-principle for allele-specific silencing in the central nervous system
URI: http://hdl.handle.net/10316/12776
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0003341
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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