Non-viral gene editing to fix cystic fibrosis stop mutations
Combinatorial design of nonviral base editing systems for treating cystic fibrosis with nonsense mutations
This project tests inhaled, non-viral gene editing to correct premature 'stop' mutations in the CFTR gene for people with cystic fibrosis caused by nonsense mutations.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Toronto NIH-funded |
| Lab location | 1 site (Toronto, Canada) |
| Project ID | NIH-11320879 on NIH RePORTER |
What this research studies
If I had cystic fibrosis from a nonsense (premature stop) mutation, researchers would try to restore my CFTR protein by using RNA versions of adenine base editors packaged into lipid nanoparticles that can be delivered to the lungs. They will chemically optimize the base editor RNA to improve precision and editing efficiency. The team will develop and test inhalable lipid nanoparticle formulations to get the editors into lung cells. Finally, they will test safety and whether CFTR function is restored in mouse models that carry CFTR nonsense mutations before any human work.
Who could benefit from this research
Good fit: Ideal candidates would be people with cystic fibrosis who carry CFTR nonsense (premature stop) mutations and who meet health criteria for future lung-directed experimental therapies.
Not a fit: People whose CF is caused by other mutation types (for example F508del or many missense mutations), or those with advanced lung disease or contraindications to inhaled nanoparticle therapies, may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could restore functional CFTR protein in people with CF caused by nonsense mutations, potentially improving lung and pancreatic function and reducing complications.
How similar studies have performed: Base editing and lipid-nanoparticle delivery have shown encouraging results in cells and animal models, but using non-viral adenine base editors delivered to the lung for CF nonsense mutations is largely a novel, preclinical approach.
Where this research is happening
Toronto, Canada
- University of Toronto — Toronto, Canada (Active)
Researchers
- Principal investigator: Li, Bowen — University of Toronto
- Study coordinator: Li, Bowen
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.