Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 28. Juli, Seite 4564 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Beck, Christina [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 31.07.2023 Date Revised 01.08.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-40185-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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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| 700 | 1 | |a Vaccarello, Paula |e verfasserin |4 aut | |
| 700 | 1 | |a Widenmeyer, Florenc |e verfasserin |4 aut | |
| 700 | 1 | |a Feuerherd, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Cho-Chin |e verfasserin |4 aut | |
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| 700 | 1 | |a Abikeeva, Tatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Schädler, Julia |e verfasserin |4 aut | |
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| 700 | 1 | |a Frischmuth, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Engelhardt, Stefan |e verfasserin |4 aut | |
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