Gene-editing treatment for phenylketonuria caused by the P281L PAH mutation
LEAD PROJECT 1: PHENYLKETONURIA (PKU)
A lipid nanoparticle-delivered adenine base editor to correct the P281L PAH mutation in people with phenylketonuria.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Hosp of Philadelphia NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11145249 on NIH RePORTER |
What this research studies
If you or your child have PKU with the common P281L PAH mutation, this project is developing a one-time gene-editing treatment delivered to the liver using lipid nanoparticles to fix the faulty gene. The team will use an adenine base editor to change the single DNA letter responsible for the mutation without cutting both strands of DNA. Over five years they plan preclinical testing, filing an IND with the FDA, and then starting a Phase 1/2 clinical trial to check safety and effects on blood phenylalanine. The work is intended to lower lifelong dietary restrictions and reduce reliance on daily enzyme injections.
Who could benefit from this research
Good fit: Ideal candidates are people with classical phenylketonuria who have a confirmed PAH c.842C>T (P281L) mutation and who meet health criteria for an early-phase gene therapy trial.
Not a fit: People with PKU who do not carry the P281L mutation or those with advanced, irreversible neurological damage are unlikely to benefit from this targeted approach.
Why it matters
Potential benefit: If successful, the treatment could durably lower blood phenylalanine and reduce or eliminate the need for a strict low-Phe diet or frequent enzyme injections.
How similar studies have performed: Base editing delivered by lipid nanoparticles has shown promising results in preclinical models and early translational work, but correcting PAH P281L in humans is a novel application with limited clinical precedent.
Where this research is happening
Philadelphia, United States
- Children's Hosp of Philadelphia — Philadelphia, United States (Active)
Researchers
- Principal investigator: Musunuru, Kiran — Children's Hosp of Philadelphia
- Study coordinator: Musunuru, Kiran
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.