A controllable gene editor to correct heart gene mutations that cause HCM
Chemically inducible split base editors for precise and controllable in vivo genome editing
Trying a switchable gene-editing tool to precisely fix MYBPC3 mutations in adults with inherited hypertrophic cardiomyopathy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11264851 on NIH RePORTER |
What this research studies
Researchers are developing a switchable base editor that only becomes active when a chemical 'switch' brings its two parts together, to reduce unwanted editing elsewhere in the body. The system is delivered with dual AAV vectors so the editor can work inside heart cells, and the team will optimize the design to improve precision and safety. In mice the split, chemically inducible editor achieved precise edits in the liver, and the group now aims to adapt and test the approach for correcting MYBPC3 mutations that cause familial HCM. This work is currently preclinical and would require further safety and clinical testing before it could be offered to patients.
Who could benefit from this research
Good fit: Adults (21+) with hypertrophic cardiomyopathy caused by specific MYBPC3 single-nucleotide mutations would be the most likely candidates for this approach.
Not a fit: People whose HCM is not caused by MYBPC3 mutations, children under 21, or those who cannot receive AAV-based gene therapy would likely not benefit from this work.
Why it matters
Potential benefit: If successful, a single, controlled in-body treatment could correct disease-causing MYBPC3 mutations and potentially halt or reverse familial HCM in eligible patients.
How similar studies have performed: Related preclinical work showed the split, chemically controlled base editor could precisely edit the PCSK9 gene in mouse liver, but adapting this method to human heart disease is still experimental.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Gao, Xue — University of Pennsylvania
- Study coordinator: Gao, Xue
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.