PDF(Pubmed)
Abstract：
Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer\'s disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.
摘要：
致病等位基因沉默是一种有希望的治疗遗传性遗传性疾病的方法。这里,我们开发了一种RNA切割工具，TaqTth-hpRNA,由一个小的，嵌合TaqTth,和发夹RNA引导探针。具有最小的侧翼序列基序要求，体外和体内研究表明TaqTth-hpRNA能有效和特异地切割RNA。在阿尔茨海默病模型中,我们证明了突变APPswemRNA的沉默，而不改变野生型APPmRNA。值得注意的是,由于TaqTth的紧凑尺寸，我们能够在单个AAV载体中与APOE2过表达结合，这导致对病理的更强抑制。
