Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol-conjugated heteroduplex oligonucleotide in mice.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 07 2021
09 07 2021
Historique:
received:
06
11
2020
accepted:
11
06
2021
entrez:
10
7
2021
pubmed:
11
7
2021
medline:
9
11
2021
Statut:
epublish
Résumé
Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (antimiR) could be a useful strategy for treating ischemic stroke. However, few attempts have been made to achieve this strategy via systemic route due to lack of efficient delivery-method toward BECs. Here, we have developed a new technology for delivering an antimiR into BECs and silencing miRNAs in BECs, using a mouse ischemic stroke model. We designed a heteroduplex oligonucleotide, comprising an antimiR against miRNA-126 (miR-126) known as the endothelial-specific miRNA and its complementary RNA, conjugated to α-tocopherol as a delivery ligand (Toc-HDO targeting miR-126). Intravenous administration of Toc-HDO targeting miR-126 remarkably suppressed miR-126 expression in ischemic brain of the model mice. In addition, we showed that Toc-HDO targeting miR-126 was delivered into BECs more efficiently than the parent antimiR in ischemic brain, and that it was delivered more effectively in ischemic brain than non-ischemic brain of this model mice. Our study highlights the potential of this technology as a new clinical therapeutic option for ischemic stroke.
Identifiants
pubmed: 34244578
doi: 10.1038/s41598-021-93666-y
pii: 10.1038/s41598-021-93666-y
pmc: PMC8270953
doi:
Substances chimiques
MIRN126 microRNA, mouse
0
MicroRNAs
0
Oligonucleotides
0
alpha-Tocopherol
H4N855PNZ1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14237Informations de copyright
© 2021. The Author(s).
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