TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.
Genome Biol
; 25(1): 179, 2024 Jul 07.
Article
em En
| MEDLINE
| ID: mdl-38972974
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article