TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.
Genome Biol
; 25(1): 179, 2024 Jul 07.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Gene Silencing
/
Alzheimer Disease
Limits:
Animals
/
Humans
Language:
En
Journal:
Genome Biol
/
Genome biol
/
Genome biology (Online)
Year:
2024
Document type:
Article