LNP-based adenine base editing for PKU and urea cycle disorders
Official title: LEAD PROJECT 1: PHENYLKETONURIA (PKU)
Funded at Children's Hosp of Philadelphia · NIH-11421632 · Data updated 2026-11-12
A front-line, patient-focused research project aims to develop safe gene-editing therapies that could lessen or correct the biochemical problems in PKU and related urea cycle disorders.
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 start | August 1, 2023 |
| Project end | July 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $5,455,342 |
| NIH project number | 3U19NS132301-04S1 |
| Project ID | NIH-11421632 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are individuals with PKU or urea cycle disorders eligible for early-phase clinical trials.
✕Less likely to help
Patients without these specific conditions or who are not eligible for early-stage trials may not benefit.
What this research studies
This program targets inherited disorders where harmful DNA changes cause high levels of phenylalanine or ammonia. It plans to use lipid nanoparticles to deliver adenine base editors to correct these genetic defects, with steps toward filing an IND and testing in a phase I/II master protocol. If successful, people with PKU or UCDs could have a future treatment that addresses the root genetic cause. The research is led by Children’s Hospital of Philadelphia and will follow a multi-year plan to move from preclinical work to early human studies.
Why it matters
Potential benefit: If successful, this approach could provide a transformative treatment that reduces neurotoxic buildup and improves health outcomes for PKU and UCD patients.
How similar studies have gone: Previous work has shown promise with base-editing approaches in other genetic conditions; this plan advances toward clinical testing in PKU/UCDs.
Where this research is happening
-
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
Related research
Other NIH-funded projects on the same topics.
-
PKU: a new gene-editing treatment for a common PAH mutation
A new therapy using lipid nanoparticles to correct a common PKU mutation could reduce the need for strict diets and dangerous enzyme injections.
-
A new gene-editing approach to treat phenylketonuria (PKU)
A medical research project is testing a gene-editing strategy using AAV-delivered CRISPR tools to correct PAH gene defects in PKU patients.
-
Phenylalanine and brain function in PKU carriers and non-carriers
We’re exploring how a single elevated nutrient (phenylalanine) affects thinking and brain function in adults who carry a PKU gene variant compared with those who don’t.
-
Gene-editing treatment for phenylketonuria caused by the P281L PAH mutation
A lipid nanoparticle-delivered adenine base editor to correct the P281L PAH mutation in people with phenylketonuria.
-
Using gene editing to treat phenylketonuria
This study is exploring a new way to use gene editing to help people with phenylketonuria (PKU) by fixing the genetic issues that cause the condition, aiming to offer a better treatment than the current strict diets and medications.
-
Investigating how elevated phenylalanine affects brain and cognitive function in adults who carry the PKU gene.
This study is looking at how higher levels of phenylalanine (Phe) might affect thinking and brain function in adults who carry the PKU gene but don’t have the condition, to help us understand if they might face any challenges related to Phe.
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.