In vivo editing of lung stem cells for durable gene correction in mice

Intravenously administered gene-editing lipid nanoparticles achieved >70% lung stem cell editing in mice, maintaining expression for 660 days.

• High levels of genome editing were achieved in stem cells using optimized lung-targeting lipid nanoparticles.
• Sustained tdTomato expression was observed in over 80% of lung epithelial cells for nearly two years.
• In cystic fibrosis cases, the gene-editing approach corrected over 95% of cystic fibrosis transmembrane conductance regulator (CFTR) DNA.
• Restoration of CFTR function in patient-derived bronchial epithelial cells was comparable to the standard treatment, Trikafta.
• Successful correction of intestinal organoids and R553X nonsense mutations occurred in 50% of lung stem cells in cystic fibrosis mice.

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