Gene therapies that use natural RNA splicing to keep treatment active in muscle but off elsewhere
Smarter gene therapies: alternative splicing cassettes for tissue-and self-regulated cargo expression
This project develops gene therapy tools that use alternative RNA splicing to turn therapeutic genes on in skeletal muscle but keep them off in heart and other tissues for people with Duchenne muscular dystrophy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Florida NIH-funded |
| Lab location | 1 site (Gainesville, United States) |
| Project ID | NIH-11240303 on NIH RePORTER |
What this research studies
This project will create “splicing” switches that can be packaged into AAV gene therapy to favor expression in skeletal muscle while de-targeting heart and other organs. Researchers will insert muscle-specific exons and 3'UTR elements into AAV cargoes and test these constructs in cell and animal models to measure where the gene turns on and whether it reduces toxic effects in liver and dorsal root ganglia. They will use bioinformatics to choose the best splicing elements and iteratively optimize the cassettes for stronger muscle-only expression. The goal is to produce safer, self-regulating expression systems that could be moved toward human testing.
Who could benefit from this research
Good fit: People with Duchenne muscular dystrophy who might be candidates for future AAV gene therapies or who are interested in participating in translational gene-therapy research would be the most relevant group.
Not a fit: Patients with conditions unrelated to muscle gene replacement, or those whose mutations are not amenable to AAV-mediated gene replacement or who have prohibitive pre-existing immunity to AAV, are unlikely to benefit directly from this work.
Why it matters
Potential benefit: If successful, this work could make gene replacement safer and more effective for Duchenne patients by limiting harmful expression in non-muscle tissues.
How similar studies have performed: AAV gene replacement has produced promising results in some settings, but using alternative splicing cassettes to fine-tune tissue-specific expression is a newer strategy with limited prior clinical testing.
Where this research is happening
Gainesville, United States
- University of Florida — Gainesville, United States (Active)
Researchers
- Principal investigator: Wang, Eric T — University of Florida
- Study coordinator: Wang, Eric T
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.