| First Author | Sun Y | Year | 2024 |
| Journal | Science | Volume | 384 |
| Issue | 6701 | Pages | 1196-1202 |
| PubMed ID | 38870301 | Mgi Jnum | J:359278 |
| Mgi Id | MGI:7705600 | Doi | 10.1126/science.adk9428 |
| Citation | Sun Y, et al. (2024) In vivo editing of lung stem cells for durable gene correction in mice. Science 384(6701):1196-1202 |
| abstractText | In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction. |
