{Reference Type}: Journal Article
{Title}: TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.
{Author}: Xu C;Cao J;Qiang H;Liu Y;Wu J;Luo Q;Wan M;Wang Y;Wang P;Cheng Q;Zhou G;Sima J;Guo Y;Xu S;
{Journal}: Genome Biol
{Volume}: 25
{Issue}: 1
{Year}: 2024 Jul 7
暂无{DOI}: 10.1186/s13059-024-03326-3
{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.