Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 07 2023
28 07 2023
Historique:
received:
23
12
2022
accepted:
18
07
2023
medline:
31
7
2023
pubmed:
29
7
2023
entrez:
28
7
2023
Statut:
epublish
Résumé
Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.
Identifiants
pubmed: 37507393
doi: 10.1038/s41467-023-40185-1
pii: 10.1038/s41467-023-40185-1
pmc: PMC10382532
doi:
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4564Informations de copyright
© 2023. The Author(s).
Références
Nat Commun. 2020 Jul 16;11(1):3559
pubmed: 32678092
Lancet. 2022 Oct 1;400(10358):1157-1170
pubmed: 36070788
Nature. 2022 May;605(7911):640-652
pubmed: 35361968
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
J Vis Exp. 2019 Feb 12;(144):
pubmed: 30829341
Sci Adv. 2018 Oct 17;4(10):eaat3386
pubmed: 30345352
Curr Opin Struct Biol. 2022 Aug;75:102394
pubmed: 35617912
JAMA. 2018 Feb 20;319(7):698-710
pubmed: 29466596
J Clin Invest. 2022 Jun 1;132(11):
pubmed: 35642640
Nat Rev Immunol. 2020 Feb;20(2):95-112
pubmed: 31558839
Nat Rev Microbiol. 2021 Jul;19(7):409-424
pubmed: 34075212
Immunity. 2013 Jan 24;38(1):79-91
pubmed: 23273845
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nucleic Acids Res. 2012 Jan;40(1):37-52
pubmed: 21911355
Nature. 2022 Jun;606(7914):585-593
pubmed: 35483404
Nature. 2021 Jul;595(7865):114-119
pubmed: 33915568
Biology (Basel). 2012 Dec 14;1(3):895-905
pubmed: 24832523
Nucleic Acids Res. 2022 Jul 5;50(W1):W611-W615
pubmed: 35489057
Nat Immunol. 2022 Feb;23(2):194-202
pubmed: 35105985
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Circulation. 2021 Apr 13;143(15):1513-1525
pubmed: 33550817
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Rev Immunol. 2020 Jun;20(6):355-362
pubmed: 32376901
J Leukoc Biol. 2012 Dec;92(6):1177-86
pubmed: 22966131
Immunity. 2022 Sep 13;55(9):1564-1580
pubmed: 36103853
Nucleic Acids Res. 2022 May 20;50(9):4840-4859
pubmed: 35524566
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell. 2005 Jan 14;120(1):15-20
pubmed: 15652477
Lancet. 2022 Oct 1;400(10358):1145-1156
pubmed: 36070787
Cell. 2021 Dec 22;184(26):6243-6261.e27
pubmed: 34914922
Nature. 2021 Jul;595(7865):107-113
pubmed: 33915569
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836