Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle.
antimiRNA
argininocalix[4]arenes
cell transfection
cell-penetrating agents
miRNA delivery
miRNA targeting
miRNA therapeutics.
microRNAs
multivalent ligands
premiRNA
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
06 Dec 2019
06 Dec 2019
Historique:
received:
22
01
2019
revised:
23
08
2019
accepted:
17
09
2019
pubmed:
17
11
2019
medline:
17
11
2019
entrez:
17
11
2019
Statut:
ppublish
Résumé
MicroRNAs (miRNAs) are short non-coding RNA molecules acting as gene regulators by repressing translation or by inducing degradation of the target RNA transcripts. Altered expression of miRNAs may be involved in the pathogenesis of many severe human diseases, opening new avenues in the field of therapeutic strategies, i.e., miRNA targeting or miRNA mimicking. In this context, the efficient and non-toxic delivery of premiRNA and antimiRNA molecules might be of great interest. The aim of the present paper is to determine whether an argininocalix[4]arene is able to efficiently deliver miRNA, premiRNA, and antimiRNA molecules to target cells, preserving their biological activity. This study points out that (1) the toxicity of argininocalix[4]arene 1 is low, and it can be proposed for long-term treatment of target cells, being that this feature is a pre-requisite for the development of therapeutic protocols; (2) the delivery of premiRNA and antimiRNA molecules is efficient, being higher when compared with reference gold standards available; and (3) the biological activity of the premiRNAs and antimiRNAs is maintained. This was demonstrated using the argininocalix[4]arene 1 in miRNA therapeutic approaches performed on three well-described experimental model systems: (1) the induction of apoptosis by antimiR-221 in glioma U251 cells; (2) the induction of apoptosis by premiR-124 in U251 cells; and (3) the inhibition of pro-inflammatory IL-8 and IL-6 genes in cystic fibrosis IB3-1 cells. Our results demonstrate that the argininocalix[4]arene 1 should be considered a very useful delivery system for efficient transfer to target cells of both premiRNA and antimiRNA molecules, preserving their biological activity.
Identifiants
pubmed: 31733592
pii: S2162-2531(19)30300-2
doi: 10.1016/j.omtn.2019.09.029
pmc: PMC6859282
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
748-763Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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