One-time gene-editing therapy for hereditary tyrosinemia type 1
PROJECT 2: HEREDITARY TYROSINEMIA TYPE 1 (HT1)
A one-time gene-editing treatment using lipid nanoparticles and adenine base editors aimed at fixing the genetic cause of hereditary tyrosinemia type 1 in newborns and children.
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-11145250 on NIH RePORTER |
What this research studies
This project is developing a one-time therapy that delivers an adenine base editor to the liver using lipid nanoparticles to inactivate the HPD gene that contributes to toxic metabolite buildup in HT1. The team plans a postnatal clinical program with the goal of filing an IND and starting a human trial, while also performing preclinical studies of prenatal delivery approaches. Researchers will measure where the treatment goes in the body, how effectively it edits the target gene, and safety outcomes to support regulatory review. If the postnatal approach proves safe and effective, prenatal strategies may be advanced toward human testing in the future.
Who could benefit from this research
Good fit: Ideal candidates are infants or children with genetically confirmed HT1 (FAH deficiency), particularly those who struggle with daily NTBC therapy or face high risk of liver complications.
Not a fit: People without HT1 or patients with advanced, end-stage liver failure already requiring transplant would not be expected to benefit from this therapy.
Why it matters
Potential benefit: If successful, this could provide a one-time, lifelong treatment that reduces or eliminates the need for twice-daily NTBC and lowers the risk of liver failure and cancer.
How similar studies have performed: Lipid nanoparticle delivery of in vivo gene editors has shown promising results in animal studies and early human trials for other liver disorders, but adenine base editing for HT1 and prenatal editing approaches are largely novel.
Where this research is happening
Philadelphia, United States
- Children's Hosp of Philadelphia — Philadelphia, United States (Active)
Researchers
- Principal investigator: Peranteau, William H. — Children's Hosp of Philadelphia
- Study coordinator: Peranteau, William H.
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.