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

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Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage. / Beck, Christina; Ramanujam, Deepak; Vaccarello, Paula; Widenmeyer, Florenc; Feuerherd, Martin; Cheng, Cho-Chin; Bomhard, Anton; Abikeeva, Tatiana; Schädler, Julia; Sperhake, Jan-Peter; Graw, Matthias; Safi, Seyer; Hoffmann, Hans; Staab-Weijnitz, Claudia A; Rad, Roland; Protzer, Ulrike; Frischmuth, Thomas; Engelhardt, Stefan.

In: NAT COMMUN, Vol. 14, No. 1, 4564, 28.07.2023.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, CA, Rad, R, Protzer, U, Frischmuth, T & Engelhardt, S 2023, 'Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage', NAT COMMUN, vol. 14, no. 1, 4564. https://doi.org/10.1038/s41467-023-40185-1

APA

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. (2023). Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage. NAT COMMUN, 14(1), [4564]. https://doi.org/10.1038/s41467-023-40185-1

Vancouver

Beck C, Ramanujam D, Vaccarello P, Widenmeyer F, Feuerherd M, Cheng C-C et al. Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage. NAT COMMUN. 2023 Jul 28;14(1). 4564. https://doi.org/10.1038/s41467-023-40185-1

Bibtex

@article{606ece78dad54061adf2791a317a3a3a,
title = "Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage",
abstract = "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.",
keywords = "Mice, Humans, Animals, COVID-19/pathology, SARS-CoV-2, Lung/pathology, Macrophages, Pneumonia/pathology, MicroRNAs/genetics, Fibrosis",
author = "Christina Beck and Deepak Ramanujam and Paula Vaccarello and Florenc Widenmeyer and Martin Feuerherd and Cho-Chin Cheng and Anton Bomhard and Tatiana Abikeeva and Julia Sch{\"a}dler and Jan-Peter Sperhake and Matthias Graw and Seyer Safi and Hans Hoffmann and Staab-Weijnitz, {Claudia A} and Roland Rad and Ulrike Protzer and Thomas Frischmuth and Stefan Engelhardt",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = jul,
day = "28",
doi = "10.1038/s41467-023-40185-1",
language = "English",
volume = "14",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage

AU - Beck, Christina

AU - Ramanujam, Deepak

AU - Vaccarello, Paula

AU - Widenmeyer, Florenc

AU - Feuerherd, Martin

AU - Cheng, Cho-Chin

AU - Bomhard, Anton

AU - Abikeeva, Tatiana

AU - Schädler, Julia

AU - Sperhake, Jan-Peter

AU - Graw, Matthias

AU - Safi, Seyer

AU - Hoffmann, Hans

AU - Staab-Weijnitz, Claudia A

AU - Rad, Roland

AU - Protzer, Ulrike

AU - Frischmuth, Thomas

AU - Engelhardt, Stefan

N1 - © 2023. The Author(s).

PY - 2023/7/28

Y1 - 2023/7/28

N2 - 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.

AB - 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.

KW - Mice

KW - Humans

KW - Animals

KW - COVID-19/pathology

KW - SARS-CoV-2

KW - Lung/pathology

KW - Macrophages

KW - Pneumonia/pathology

KW - MicroRNAs/genetics

KW - Fibrosis

U2 - 10.1038/s41467-023-40185-1

DO - 10.1038/s41467-023-40185-1

M3 - SCORING: Journal article

C2 - 37507393

VL - 14

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 4564

ER -