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Nucleic Acid Ther ; 32(4): 300-311, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35612431

RESUMEN

We evaluated the potential of AGTR1, the principal receptor for angiotensin II (Ang II) and a member of the G protein-coupled receptor family, for targeted delivery of antisense oligonucleotides (ASOs) in cells and tissues with abundant AGTR1 expression. Ang II peptide ASO conjugates maintained robust AGTR1 signaling and receptor internalization when ASO was placed at the N-terminus of the peptide, but not at C-terminus. Conjugation of Ang II peptide improved ASO potency up to 12- to 17-fold in AGTR1-expressing cells. Additionally, evaluation of Ang II conjugates in cells lacking AGTR1 revealed no enhancement of ASO potency. Ang II peptide conjugation improves potency of ASO in mouse heart, adrenal, and adipose tissues. The data presented in this report add to a growing list of approaches for improving ASO potency in extrahepatic tissues.


Asunto(s)
Oligonucleótidos Antisentido , Receptor de Angiotensina Tipo 1 , Animales , Ratones , Oligonucleótidos Antisentido/farmacología , Receptor de Angiotensina Tipo 1/genética , Transducción de Señal
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