Gymnotic uptake of AntimiRs alter microRNA-34a levels in 2D and 3D epithelial cell culture.
AMO
MT: Oligonucleotides: Therapies and Applications
antimiRs
epithelium
imaging
lung
miR-34a
miRNA
therapeutic oligonucleotides
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:
12 Sep 2023
12 Sep 2023
Historique:
received:
24
03
2023
accepted:
14
08
2023
medline:
8
9
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
MicroRNAs are attractive therapeutic targets in many diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Among microRNA inhibitors antimiRs have been proven successful in lowering aberrant microRNA levels in the clinic. We present a set of antimiRs targeting miR-34a, which has been shown to be dysregulated in chronic lung diseases. The tool compounds were taken up by a bronchial epithelial cell line and primary human bronchial epithelial cells, followed by efficient knockdown of miR-34a. Similar results were observed in 3D differentiated primary human bronchial epithelial cells cultured at the air-liquid interface. Varying chemical properties of antimiRs had significant impact on cellular uptake and potency, resulting in effective tool compounds for use in lung-relevant cellular systems. This report demonstrates gymnotic antimiR uptake and activity in 3D epithelial cell culture after apical administration, mimicking inhalation conditions.
Identifiants
pubmed: 37680982
doi: 10.1016/j.omtn.2023.08.014
pii: S2162-2531(23)00224-X
pmc: PMC10480572
doi:
Types de publication
Journal Article
Langues
eng
Pagination
898-907Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
All authors are AstraZeneca employees.
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