A new gene-editing approach to treat phenylketonuria (PKU)
Official title: Corrective editing to treat phenylketonuria
Funded at University of Pennsylvania · NIH-11332257 · Data updated 2026-11-12
A medical research project is testing a gene-editing strategy using AAV-delivered CRISPR tools to correct PAH gene defects in PKU patients.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project start | June 5, 2024 |
| Project end | May 31, 2029 |
| Funding year | 2026 |
| Award (this year) | $675,157 |
| NIH project number | 5R01HD110733-03 |
| Project ID | NIH-11332257 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with PKU, especially those with PAH mutations like R408W who have limited responses to existing therapies, may be candidates for future translation.
✕Less likely to help
Some PKU patients may not benefit in the early phases due to safety concerns or variant-specific limitations of the editing approach.
What this research studies
This project explores using CRISPR-based gene editing to fix mutations in the PAH gene, aiming for durable or curative results for PKU. Researchers plan to use an AAV delivery system to introduce precise edits and potentially restore normal PAH function. The study will build on current PKU therapies by pursuing a one-time or long-lasting intervention that could reduce or eliminate the need for strict diets or ongoing medications. Participation would involve early-phase testing related to safety and feasibility, with a focus on how well the editing works in relevant tissues and any immune responses. The effort reflects a careful step toward translating gene-editing advances into real-world benefits for PKU patients.
Why it matters
Potential benefit: If successful, this approach could provide a lasting correction of PAH mutations, reducing reliance on strict diets and improving cognitive and neuropsychiatric outcomes for PKU patients.
How similar studies have gone: Gene-editing approaches for PKU and other inherited metabolic disorders have shown proof-of-concept in preclinical studies, with ongoing exploration in humans.
Where this research is happening
-
University of Pennsylvania
Philadelphia, United States Active
Researchers
- Principal investigator: Wang, Xiao — University of Pennsylvania
- Study coordinator: Wang, Xiao
Related research
Other NIH-funded projects on the same topics.
-
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.
-
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.
-
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.