Targeted Delivery of Antisense Oligonucleotides Through Angiotensin Type 1 Receptor.

IF 4 2区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nucleic acid therapeutics Pub Date : 2022-05-24 DOI:10.1089/nat.2021.0105

Carol Kuo, Mehran Nikan, S. Yeh, A. Chappell, M. Tanowitz, P. Seth, T. P. Prakash, A. Mullick

引用次数: 2

Abstract

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.

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反义寡核苷酸通过血管紧张素1型受体的靶向递送。

AGTR1是血管紧张素II (Ang II)的主要受体，也是G蛋白偶联受体家族的一员，我们评估了AGTR1在AGTR1表达丰富的细胞和组织中靶向递送反义寡核苷酸(aso)的潜力。当ASO被放置在肽的n端而不是c端时，Ang II肽ASO偶联物保持了强大的AGTR1信号传导和受体内化。在agtr1表达细胞中偶联Ang II肽可使ASO效价提高12- 17倍。此外，在缺乏AGTR1的细胞中对Ang II偶联物的评估显示ASO效力没有增强。angii肽偶联提高ASO在小鼠心脏、肾上腺和脂肪组织中的效力。本报告中提供的数据为提高ASO在肝外组织中的效力提供了越来越多的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nucleic acid therapeutics BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

7.60

自引率

7.50%

发文量

审稿时长

>12 weeks

期刊介绍： Nucleic Acid Therapeutics is the leading journal in its field focusing on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. The Journal examines many new approaches for using nucleic acids as therapeutic agents or in modifying nucleic acids for therapeutic purposes including: oligonucleotides, gene modification, aptamers, RNA nanoparticles, and ribozymes.