Tailor-made RNAi knockdown against triplet repeat disease-causing alleles |
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Authors: | Takahashi Masaki Watanabe Shoko Murata Miho Furuya Hirokazu Kanazawa Ichiro Wada Keiji Hohjoh Hirohiko |
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Affiliation: | National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan. |
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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. |
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Keywords: | disease allele-specific silencing Huntington disease |
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