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Specific silencing of pathogenic mRNA by a novel compact RNA-targeting tool TaqTth-hpRNA [RNA-seq]

GSE269592 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/06/20 Platform GPL20301
Summary
Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. However, the concern about the specificity of present RNA-knockdown strategies has limited their in vivo applications. Here a TaqTth-hpRNA system consisting of a small, chimeric protein (TaqTth) and hairpin-RNA probe (hpRNA) is provided. The TaqTth-hpRNA showed a high-specific knockdown against targeted mRNA with minimal flanking sequence-motif requirement and less cell viability damage, then was applied to mutant APPswe mRNA silencing without altering the wild-type APP mRNA in Alzheimer’s disease. Notably, the combination of the TaqTth and human apolipoprotein E 2 (APOE2) overexpression encoded in a single AAV vector is available due to the compact size of TaqTth, and showed stronger inhibition of pathologies in the mouse model. Altogether, we provided the basis for a small RNA-targeting tool with high selectivity, minimal flanking sequence-motif requirement, less cell viability damage and potentially being an alternative in therapeutic applications.
Published in
TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA
Xu C, Cao J, Qiang H et al. · Genome biology 2024 · PMID 38972974 · doi:10.1186/s13059-024-03326-3
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Also filed as BioProject PRJNA1121589 and SRA study SRP512699. Searching any of these in the dataset finder brings you back here.

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