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Beck, C.* ; Ramanujam, D.* ; Vaccarello, P.* ; Widenmeyer, F.* ; Feuerherd, M. ; Cheng, C.C.* ; Bomhard, A.* ; Abikeeva, T.* ; Schädler, J.* ; Sperhake, J.P.* ; Graw, M.* ; Safi, S.* ; Hoffmann, H.* ; Staab-Weijnitz, C.A. ; Rad, R.* ; Protzer, U. ; Frischmuth, T.* ; Engelhardt, S.*

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.

Nat. Commun. 14:4564 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genes
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 4564 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30203 - Molecular Targets and Therapies
80000 - German Center for Lung Research
30202 - Environmental Health
Research field(s) Immune Response and Infection
Lung Research
PSP Element(s) G-502700-003
G-501800-817
G-501600-001
G-502799-701
Grants DFG
European Union
BMBF
Bayerische Forschungsstiftung through CoVmiR
Deutsche Forschungsgemeinschaft (DFG)
German Federal Ministry of Education and Research BMBF
Freiburg Galaxy Team: Bjoern Gruening, Bioinformatics, University of Freiburg (Germany) - Collaborative Research Centre 992 Medical Epigenetics (DFG)
DOI 10.1038/s41467-023-40185-1
WOS ID 001040551400011
Scopus ID 85165974849
PubMed ID 37507393
Erfassungsdatum 2023-10-06
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