Lung-Accumulating Mucin 5AC Silencing by Noninflammatory Lipid Nanoparticles for Asthma Treatment - PubMed
3 days ago
- #lipid nanoparticles
- #MUC5AC
- #asthma treatment
- Overexpression of Mucin 5AC (MUC5AC) leads to excessive mucus secretion, contributing to severe asthma and mucous obstructive lung diseases (MOLDs).
- FDA-approved lipid nanoparticle (LNP) carriers for siRNA delivery can paradoxically increase MUC5AC due to inflammatory side effects.
- Researchers designed noninflammatory LNPs by developing low-immunogenicity ionizable lipids, incorporating anti-inflammatory compounds, and reducing the N/P ratio.
- A lead LNP formulation (Formulation 1) achieved 85% MUC5AC silencing in vivo, outperforming integrin αvβ6 ligand-modified siRNA (69%).
- Formulation 1 demonstrated improved biosafety compared to SM102 and MC3 LNPs.
- In HDM-induced asthmatic mice, siMuc5ac-LNPs alleviated airway inflammation and obstruction with sustained preventive effects.
- Formulation 1 also suppressed MUC5AC secretion in a COPD patient-derived organoid model.
- The study presents a clinically translatable, noninflammatory siRNA delivery platform for asthma and other MOLDs.