Boosting JAG1 by fixing DNA switches in Alagille Syndrome
Mapping, programming, and correcting gene regulatory sequences for Alagille Syndrome
This project will reprogram DNA 'switches' so cells in people with Alagille Syndrome make more of the JAG1 protein.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Stanford University NIH-funded |
| Lab location | 1 site (Stanford, United States) |
| Project ID | NIH-11229728 on NIH RePORTER |
What this research studies
From my perspective as a patient, the team is mapping the DNA 'switches' that control JAG1 and testing precise edits to those switches using high-throughput CRISPR tools. They will use cell models that represent blood vessel and liver cells to find edits that raise JAG1 levels without disrupting other genes. Promising edits will be refined and tested for their ability to correct harmful gene-expression patterns seen in Alagille Syndrome. If lab results are encouraging, the work could progress toward using patient samples and early clinical testing.
Who could benefit from this research
Good fit: People with genetically confirmed Alagille Syndrome due to JAG1 haploinsufficiency, or individuals willing to donate blood or skin samples for lab studies, would be the most relevant candidates.
Not a fit: Patients whose symptoms are caused by other genes (for example NOTCH2) or those who cannot receive gene-based therapies are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this approach could increase production of the healthy JAG1 copy and help prevent or lessen the liver and heart complications of Alagille Syndrome.
How similar studies have performed: CRISPR-based editing of regulatory DNA has shown promise in lab models for other conditions, but programming promoters to boost a patient's own allele in Alagille Syndrome is largely novel and not yet tested in patients.
Where this research is happening
Stanford, United States
- Stanford University — Stanford, United States (Active)
Researchers
- Principal investigator: Engreitz, Jesse M — Stanford University
- Study coordinator: Engreitz, Jesse M
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.