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| Status |
Public on Jul 12, 2023 |
| Title |
Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [transcriptome_human_COVID] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Recent studies of severe acute inflammatory lung disease including COVID-19 have identified 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 was among the strongest upregulated microRNAs in COVID-19 and in mice with acute inflammatory lung damage and was the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of an oligonucleotide inhibitor of microRNA-21 to trimannose achieved rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reversed pathological activation of macrophages and prevented pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevented 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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| Overall design |
Here, we sequenced human post mortem lungs (COVID-19 and controls) and fresh human lungs infected with SARS-CoV-2 (+Treatment with RCS-21).
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| Contributor(s) |
Beck C, Ramanujam D, Engelhardt S |
| Citation(s) |
37507393 |
| Submission date |
Jun 16, 2023 |
| Last update date |
Oct 12, 2023 |
| Contact name |
Stefan Engelhardt |
| Organization name |
Technical University Munich
|
| Department |
Institute of Pharmacology and Toxicology
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| Street address |
Biedersteiner Str. 29
|
| City |
Munich |
| ZIP/Postal code |
80802 |
| Country |
Germany |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
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| Samples (42)
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| This SubSeries is part of SuperSeries: |
| GSE235136 |
Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage |
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| Relations |
| BioProject |
PRJNA984658 |
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