Compact CRISPR-based activation to target lung vascular enhancers in a mouse model
Official title: Targeting Undruggable Lung Vascular Enhancers with Compact AAV-Cas12f CRISPR Activation
Funded at Cincinnati Childrens Hosp Med Ctr · NIH-11439727 · Data updated 2026-11-12
A tiny CRISPR-based gene-activation system delivered by AAV aims to turn on specific lung gene enhancers to treat alveolar capillary dysplasia and related lung conditions in a mouse model.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cincinnati Childrens Hosp Med Ctr NIH-funded |
| Lab location | 1 site (Cincinnati, United States) |
| Project start | September 1, 2026 |
| Project end | August 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $445,500 |
| NIH project number | 1R21HD123012-01 |
| Project ID | NIH-11439727 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with alveolar capillary dysplasia or related pulmonary vascular conditions could potentially benefit from future translation of this enhancer-activation strategy.
✕Less likely to help
Patients without alveolar capillary dysplasia or related lung vascular diseases may not benefit from this specific enhancer-activation approach.
What this research studies
This project will develop a small, self-contained AAV CRISPR activation tool using AsCas12f to modulate regulatory DNA elements in the lung. Researchers will optimize guide RNA layout and enhancer targeting to activate the FOXF1 enhancer in vivo and study how enhancer architecture affects efficiency and specificity. They will use reporter mice to map activation rules and then test therapeutic potential in a Foxf1-S52F mouse model that mimics human alveolar capillary dysplasia and pulmonary hypertension.
Why it matters
Potential benefit: If successful, this approach could provide a new way to treat certain severe lung vascular diseases by activating disease-relevant gene enhancers.
How similar studies have gone: Previous work shows that targeted enhancer activation can modulate gene expression in vivo, with ongoing efforts to refine specificity and delivery.
Where this research is happening
-
Cincinnati Childrens Hosp Med Ctr
Cincinnati, United States Active
Researchers
- Principal investigator: Wang, Guolun — Cincinnati Childrens Hosp Med Ctr
- Study coordinator: Wang, Guolun
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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.