Inhalable Lipid Nanoparticles for Macrophage-Specific STING Gene Editing to Ameliorate Pulmonary Fibrosis - PubMed
5 days ago
- #lipid nanoparticles
- #pulmonary fibrosis
- #CRISPR
- Inhalable lipid nanoparticles (LNPs) developed for macrophage-specific STING gene editing to treat pulmonary fibrosis.
- The STING signaling pathway in alveolar macrophages is a key driver of fibrosis.
- Optimized LNP formulation (mCas9/gSting@DOPS) shows 7-fold greater macrophage expression efficiency than commercial options.
- LNPs use phosphatidylserine (PS) for selective uptake and deliver CRISPR/Cas9 mRNA for precise Sting1 gene editing.
- Inhalation of LNPs in a murine model led to selective accumulation in macrophages, reduced pro-fibrotic cytokines, and attenuated fibrosis.
- Treatment improved survival, reduced collagen deposition, and remodeled the fibrotic immune microenvironment without systemic toxicity.