Establishment of a novel RNAi knockdown targeting nucleotide variations in neurodegenerative disease-causing alleles.

RNAi(等位基因特异性RNAi：ASP-RNAi)是RNAi技术的一种高级应用，可以特异性地抑制感兴趣的等位基因的表达。因此，ASP-RNAi在治疗上是有用的，可以特异性地抑制致病等位基因的表达，而不抑制相应的野生型等位基因的表达。为了实现ASP-RNAi，设计具有等位基因识别功能的小干扰RNA(SiRNAs)至关重要。我们开发了一种简单的带有报告等位基因的检测系统。利用我们的检测系统，我们成功地设计并筛选了针对突变的Prion蛋白(PRNP)和Huntingtin(HTT)基因的携带ASP-RNAi的合格siRNAs。

Allele-specific gene silencing by RNAi (allele-specific RNAi : ASP-RNAi) is an advanced application of RNAi techniques, by which the expression of an allele of interest can be specifically inhibited. Thus, ASP-RNAi is therapeutically useful for specifically inhibiting the expression of disease-causing alleles without suppressing the expression of corresponding wild-type alleles. To achieve ASP-RNAi, it is vital to design small interfering RNAs (siRNAs) conferring allele discrimination. We developed an easy assay system with reporter alleles. Using our assay system, we successfully designed and selected competent siRNAs conferring ASP-RNAi against mutant Prion Protein (PRNP) and Huntingtin (HTT) genes.