2025-07-03 イェール大学
<関連情報>
- https://news.yale.edu/2025/07/03/cure-cystic-fibrosis-might-start-womb
- https://www.pnas.org/doi/10.1073/pnas.2418731122
嚢胞性線維症の治療法としての子宮内遺伝子編集法 Systemic in utero gene editing as a treatment for cystic fibrosis
Adele S. Ricciardi, Christina Barone, Rachael Putman, +14 , and Marie E. Egan
Proceedings of the National Academy of Sciences Published:June 10, 2025
DOI:https://doi.org/10.1073/pnas.2418731122
Significance
Cystic fibrosis (CF), a monogenic disease resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene, affects multiple organs, including the respiratory, gastrointestinal, and reproductive systems. Irreversible pathology in these tissues is often already present at birth, suggesting that a true curative therapy would require intervention during fetal development. Here, we demonstrate CFTR gene correction in multiple tissues affected by CF after a single in utero administration of nanoparticles containing gene editing cargo. We found that gene correction was durable into adulthood in mice, which resulted in functional CFTR activity in both the respiratory and gastrointestinal systems. Our work establishes the possibility that CF could be treated, or possibly cured, by a single in utero gene editing treatment.
Abstract
In utero gene editing has the potential to modify disease-causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here, we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids encapsulated in polymeric nanoparticles and delivered systemically in utero. In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissues, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types.
