PKU: a new gene-editing treatment for a common PAH mutation
Official title: LEAD PROJECT 1: PHENYLKETONURIA (PKU)
Funded at Children's Hosp of Philadelphia · NIH-11389354 · Data updated 2026-11-12
A new therapy using lipid nanoparticles to correct a common PKU mutation could reduce the need for strict diets and dangerous enzyme injections.
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) | $1,666,159 |
| NIH project number | 4U19NS132301-04 |
| Project ID | NIH-11389354 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with PKU who carry the P281L PAH mutation and are eligible for future gene-editing therapies.
✕Less likely to help
Patients without the P281L mutation or who are not candidates for gene-editing approaches may not benefit.
What this research studies
This project aims to develop an RNA-guided base editing approach delivered by lipid nanoparticles to fix the c.842C>T (P281L) PAH mutation in people with PKU. The goal is to move toward an IND filing by year five and then start a phase 1/2 trial to test safety and early efficacy. The work involves collaboration atChildren’s Hospital of Philadelphia and will involve preclinical studies and planning for a first-in-human study. If successful, this could offer a one-time or less burdensome treatment option for patients with this genetic form of PKU.
Why it matters
Potential benefit: If successful, the approach could reduce neurotoxic phenylalanine levels and lessen treatment burden for PKU patients.
How similar studies have gone: Other approaches toward base editing for metabolic diseases show promise in preclinical work, with early clinical translation being pursued in related fields.
Where this research is happening
-
Children's Hosp of Philadelphia
Philadelphia, United States Active
Researchers
- Principal investigator: Musunuru, Kiran — Children's Hosp of Philadelphia
- Study coordinator: Musunuru, Kiran
Related research
Other NIH-funded projects on the same topics.
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LNP-based adenine base editing for PKU and urea cycle disorders
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.
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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.
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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.
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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.
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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.
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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.