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

  • Christina Beck (Geteilte/r Erstautor/in)
  • Deepak Ramanujam (Geteilte/r Erstautor/in)
  • Paula Vaccarello
  • Florenc Widenmeyer
  • Martin Feuerherd
  • Cho-Chin Cheng
  • Anton Bomhard
  • Tatiana Abikeeva
  • Julia Schädler
  • Jan-Peter Sperhake
  • Matthias Graw
  • Seyer Safi
  • Hans Hoffmann
  • Claudia A Staab-Weijnitz
  • Roland Rad
  • Ulrike Protzer
  • Thomas Frischmuth
  • Stefan Engelhardt

Beteiligte Einrichtungen

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.

Bibliografische Daten

OriginalspracheEnglisch
Aufsatznummer4564
ISSN2041-1723
DOIs
StatusVeröffentlicht - 28.07.2023

Anmerkungen des Dekanats

© 2023. The Author(s).

PubMed 37507393