Personalized liver gene editing for rare metabolic disorders
Personalized prime editing as a platform for hepatic inborn errors of metabolism
['FUNDING_U01'] · CHILDREN'S HOSP OF PHILADELPHIA · NIH-11195663
Developing a one-time, liver-delivered gene-editing treatment using AAV to correct the faulty genes that cause severe inherited liver metabolic diseases like PKU.
Quick facts
| Phase | ['FUNDING_U01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | CHILDREN'S HOSP OF PHILADELPHIA (nih funded) |
| Locations | 1 site (PHILADELPHIA, UNITED STATES) |
| Trial ID | NIH-11195663 on ClinicalTrials.gov |
What this research studies
This program is building a personalized prime-editing therapy delivered to the liver with an AAV carrier to fix a patient’s specific genetic mutation. The team plans a master protocol so safety and regulatory work done for a lead PKU therapy can speed development of follow-on therapies that only change the guide RNA sequence. In mouse models carrying a human PKU mutation, a single AAV8 prime-editing dose durably normalized blood phenylalanine levels. The work includes IND-enabling safety and manufacturing studies to prepare for future human trials.
Who could benefit from this research
Good fit: Adults with a confirmed liver-based inborn error of metabolism—especially people with PKU due to the R408W mutation or other single-gene liver enzyme defects—are the intended candidates.
Not a fit: People whose conditions are not caused by a single liver gene, those with advanced liver failure, or those ineligible for AAV-based delivery (for example due to pre-existing anti-AAV antibodies) are unlikely to benefit.
Why it matters
Potential benefit: If successful, this could permanently correct the underlying liver gene defect, lower toxic metabolites, and reduce the need for transplant or lifelong restrictive therapies.
How similar studies have performed: AAV gene therapies have shown benefit for some inherited liver diseases and prime editing has corrected mutations in animal models, but prime editing in humans remains experimental.
Where this research is happening
PHILADELPHIA, UNITED STATES
- CHILDREN'S HOSP OF PHILADELPHIA — PHILADELPHIA, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: AHRENS-NICKLAS, REBECCA CLARE — CHILDREN'S HOSP OF PHILADELPHIA
- Study coordinator: AHRENS-NICKLAS, REBECCA CLARE
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.