ArticleGene therapy2004
Long-term correction of hyperphenylalaninemia by AAV-mediated gene transfer leads to behavioral recovery in phenylketonuria mice.
Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- Article
- Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase.Materials today. Bio · 2025Article
- Amelioration of metabolic and behavioral defects through base editing in the PahMolecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Genetically humanized phenylketonuria mouse model as a testing tool for human genome editing in fertilized eggs.Journal of inherited metabolic disease · 2025Article
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Characterization of a Bioengineered AAV3B Capsid Variant with Enhanced Hepatocyte Tropism and Immune Evasion.Human gene therapy · 2023Article
- Development of an mRNA replacement therapy for phenylketonuria.Molecular therapy. Nucleic acids · 2022Article
- Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor.Science China. Life sciences · 2022Article
- Clinical, genetic, and experimental research of hyperphenylalaninemia.Frontiers in genetics · 2022Review
- Use of an adeno-associated virus serotype Anc80 to provide durable cure of phenylketonuria in a mouse model.Journal of inherited metabolic disease · 2021Article
- Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes.Science translational medicine · 2021Article
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.Molecular therapy. Methods & clinical development · 2020Article
- Split AAV-Mediated Gene Therapy Restores Ureagenesis in a Murine Model of Carbamoyl Phosphate Synthetase 1 Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Sustained Correction of a Murine Model of Phenylketonuria following a Single Intravenous Administration of AAVHSC15-PAH.Molecular therapy. Methods & clinical development · 2020Article
- Emerging Concepts and Challenges in Rheumatoid Arthritis Gene Therapy.Biomedicines · 2020Review
- Prospects for Cell-Directed Curative Therapy of Phenylketonuria (PKU).Molecular Frontiers journal · 2019Article
- State-of-the-Art 2019 on Gene Therapy for Phenylketonuria.Human gene therapy · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Classical phenylketonuria (PKU) is a metabolic disorder caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). If untreated, accumulation of phenylalanine will damage the developing brain of affected individuals, leading to severe mental retardation. Here, we show that a liver-directed PAH gene transfer brought about long-term correction of hyperphenylalaninemia and behavioral improvement in a mouse model of PKU. A recombinant adeno-associated virus (AAV) vector carrying the murine PAH cDNA was constructed and administered to PAH-deficient mice (strain PAH(enu2)) via the portal vein. Within 2 weeks of treatment, the hyperphenylalaninemic phenotype improved and completely normalized in the animals treated with higher vector doses. The therapeutic effect persisted for 40 weeks in male mice, while serum phenylalanine concentrations in female animals gradually returned to pretreatment levels. Notably, this long-term correction of hyperphenylalaninemia was associated with a reversal of hypoactivity observed in PAH(enu2) mice. While locomotory activity over 24 h and exploratory behavior were significantly decreased in untreated PAH(enu2) mice compared with the age-matched controls, these indices were completely normalized in 12-month-old male PKU mice with lowered serum phenylalanine. These results demonstrate that AAV-mediated liver transduction ameliorated the PKU phenotype, including central nervous system dysfunctions.
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