Inhaled Angiopoietin-Like 4 Antisense Oligonucleotide Therapy for Lung Injury and Fibrosis - PubMed
4 hours ago
- #host-directed therapy
- #lung fibrosis
- #antisense therapy
- Inhaled Angiopoietin-Like 4 Antisense Oligonucleotide (Angptl4-ASO) therapy targets lung injury and fibrosis by addressing coupled axes of inflammation, barrier integrity, and tissue remodeling.
- Angptl4-ASO shows efficacy in both infectious (bacterial and viral pneumonia) and fibrotic (bleomycin-induced) lung disease models by reducing inflammation, preserving alveolar architecture, and improving host defense.
- Transcriptomics reveal a shared ANGPTL4-regulated network linking hypoxic, inflammatory, apoptotic, and stress response programs, suggesting ANGPTL4 as a central regulator of injury resolution.
- Mechanistically, Angptl4-ASO reinforces epithelial barrier integrity through regulation of tight junction and glycoprotein pathways.
- Biodistribution studies confirm lung-retentive localization of Angptl4-ASO with minimal systemic dissemination over 144 hours.
- The findings position inhaled ANGPTL4-ASO as a host-directed, multi-axis therapeutic strategy for diverse pulmonary pathologies.