Amino acid-derived ionizable lipids enable inhaled base editing for therapeutic gene correction in the lung - PubMed
4 hours ago
- #Pulmonary Delivery
- #CRISPR
- #Gene Editing
- CRISPR-based gene editing offers potential for treating genetic diseases, but lung disorder applications face pulmonary delivery challenges.
- Researchers synthesized 960 ionizable lipids from proteinogenic and non-proteinogenic α-amino acids to create biodegradable nanoparticles for lung delivery.
- High-throughput screening identified CHCha-10, a cyclohexyl amino acid-derived lipid, enabling efficient mRNA-based gene editor delivery to lung epithelial cells.
- CHCha-10 nanoparticles show improved mucus penetration and epithelial-specific transfection in mice and ferrets after intratracheal administration.
- In vivo base editing via inhalation restored CFTR expression and chloride channel function in models with the CFTR G542X mutation.
- The study provides a chemical design framework for ionizable lipids and a platform for RNA-based pulmonary gene correction.