title: New RNAi strategy for selective suppression of a mutant allele in polyglutamine disease.
abstract: In gene therapy of dominantly inherited diseases with small interfering RNA (siRNA), mutant allele specific suppression may be necessary for diseases in which the defective gene normally has an important role. It is difficult, however, to design a mutant allele-specific siRNA for trinucleotide repeat diseases in which the difference of sequences is only repeat length. To overcome this problem, we use a new RNA interference (RNAi) strategy for selective suppression of mutant alleles. Both mutant and wild-type alleles are inhibited by the most effective siRNA, and wild-type protein is restored using the wild-type mRNA modified to be resistant to the siRNA. Here, we applied this method to spinocerebellar ataxia type 6 (SCA6). We discuss its feasibility and problems for future gene therapy.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kubodera
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D006801:Humans; D009154:Mutation; D010455:Peptides / Q000235:genetics*; D034622:RNA Interference; D014162:Transfection
chemical_list: D010455:Peptides; C097188:polyglutamine