Inhaled mRNA Nanoformulation with Biogenic Ribosomal Protein Reverses Established Pulmonary Fibrosis in a...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Respiratory Medicine

Background:

• Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition and alveolar epithelial cell injury.
• Current IPF treatments are limited, necessitating innovative therapeutic strategies.

Purpose of the Study:

• To develop and evaluate an inhaled mRNA nanoformulation for treating established fibrotic lung disease.
• To investigate the potential of this nanoformulation to reverse lung fibrosis by clearing matrix and promoting re-epithelialization.

Main Methods:

• Fabrication of a multi-component mRNA nanoformulation with a core, modified corona, and keratinocyte growth factor (KGF).
• Inhalation delivery of nanoformulations to a bleomycin-induced murine model of pulmonary fibrosis.
• Assessment of extracellular matrix clearance, alveolar re-epithelialization, and lung function.

Main Results:

• Inhaled nanoformulations successfully delivered mRNA to target cells within fibrotic lung lesions.
• Nanoformulations promoted clearance of collagen by increasing matrix metalloproteinase 13 (MMP13) expression.
• KGF-mediated alveolar re-epithelialization and improved lung function were observed in the treated model.

Conclusions:

• This inhaled mRNA nanoformulation strategy effectively clears lung fibrosis and promotes alveolar repair.
• The findings suggest a promising new inhalation-based delivery approach for treating idiopathic pulmonary fibrosis (IPF).