Targeted delivery of antisense oligonucleotides to pancreatic ß-cells.
Sci Adv
; 4(10): eaat3386, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-30345352
ABSTRACT
Antisense oligonucleotide (ASO) silencing of the expression of disease-associated genes is an attractive novel therapeutic approach, but treatments are limited by the ability to deliver ASOs to cells and tissues. Following systemic administration, ASOs preferentially accumulate in liver and kidney. Among the cell types refractory to ASO uptake is the pancreatic insulin-secreting ß-cell. Here, we show that conjugation of ASOs to a ligand of the glucagon-like peptide-1 receptor (GLP1R) can productively deliver ASO cargo to pancreatic ß-cells both in vitro and in vivo. Ligand-conjugated ASOs silenced target genes in pancreatic islets at doses that did not affect target gene expression in liver or other tissues, indicating enhanced tissue and cell type specificity. This finding has potential to broaden the use of ASO technology, opening up novel therapeutic opportunities, and presents an innovative approach for targeted delivery of ASOs to additional cell types.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligonucleótidos Antisentido
/
Sistemas de Liberación de Medicamentos
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Células Secretoras de Insulina
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Receptor del Péptido 1 Similar al Glucagón
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Adv
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suecia