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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE235136 | GEO | 2023/07/12

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC10382532 | biostudies-literature

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [mirnome_human_COVID]

Project description: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.

2023-07-12 | GSE235130 | GEO

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [mirnome_mouse]

2023-07-12 | GSE235132 | GEO

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [mirnome_human_basal]

2023-07-12 | GSE235131 | GEO

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [transcriptome_mouse]

2023-07-12 | GSE235134 | GEO

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [transcriptome_human_COVID]

2023-07-12 | GSE235133 | GEO

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [scRNA-seq]

2023-07-12 | GSE235135 | GEO

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

Project description:Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage

| PRJNA984645 | ENA

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [mirnome_human_COVID]

Project description:Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [mirnome_human_COVID]

| PRJNA984651 | ENA

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [transcriptome_mouse]

Project description:Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage [transcriptome_mouse]

| PRJNA984657 | ENA

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