Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone.
Nat Biomed Eng
; 4(1): 52-68, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31937944
ABSTRACT
A small percentage of the short interfering RNA (siRNA) delivered via passive lipid nanoparticles and other delivery vehicles reaches the cytoplasm of cells. The high doses of siRNA and delivery vehicle that are thus required to achieve therapeutic outcomes can lead to toxicity. Here, we show that the integration of siRNA sequences into a Dicer-independent RNA stem-loop based on pre-miR-451 microRNA-which is highly enriched in small extracellular vesicles secreted by many cell types-reduces the expression of the genes targeted by the siRNA in the liver, intestine and kidney glomeruli of mice at siRNA doses that are at least tenfold lower than the siRNA doses typically delivered via lipid nanoparticles. Small extracellular vesicles that efficiently package siRNA can significantly reduce its therapeutic dose.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
RNA Interferente Pequeno
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Vesículas Extracelulares
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biomed Eng
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá