Establishment of tailor-made RNAi knockdown technique against triplet repeat disease-causing alleles

我们提出了一种新的下拉方法来测定三联体重复致病等位基因的编码SNP （cSNP）单倍型，并证明了针对突变亨廷顿等位基因中这些cSNP位点的疾病等位基因特异性RNAi，每个等位基因都具有不同的cSNP单倍型。因此，我们的程序通过使用与疾病相关的cSNP单倍型所需的适当sirna，允许针对致病等位基因的等位基因特异性RNAi。因此，我们目前的进展为实现使用csnp作为RNAi靶点的针对三重重复疾病和其他疾病的定制RNAi治疗铺平了道路。

We present determination of the coding SNP (cSNP) haplotypes of triplet repeat disease-causing alleles by a novel pull-down method, and demonstrate disease-allele specific RNAi targeting such cSNP sites in the mutant Huntingtin alleles, each of which possesses a different cSNP haplotype. Thus, our procedures allow for allele-specific RNAi against disease-causing alleles by using appropriate siRNAs as the disease-linked cSNP haplotype demands. Therefore, our current progress paves the way to the achievement of a tailor-made RNAi treatment for triplet repeat diseases and other diseases using cSNPs as RNAi targets.