title: Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.
abstract: Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease allele-specific RNAi are quite difficult. In this study we developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and we demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP haplotype. Therefore, the methods presented here allow for allele-specific RNAi knockdown against disease-causing alleles by using siRNAs specific to disease-linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments for triplet repeat diseases.
authors.affiliation: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shoko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Furuya
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hohjoh
mesh_terms: D000483:Alleles; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018911:Trinucleotide Repeats
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering