ArticleGene therapy2006
Administration-route and gender-independent long-term therapeutic correction of phenylketonuria (PKU) in a mouse model by recombinant adeno-associated virus 8 pseudotyped vector-mediated gene transfer.
Article in Gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 82 citations in OpenAlex.
- Nutritional and Therapeutic Strategies in Paediatric Phenylketonuria: A Narrative Literature Review.Nutrients · 2026Review
- Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- Advancing Gene Therapy for Phenylketonuria: From Precision Editing to Clinical Translation.International journal of molecular sciences · 2025Review
- Experimental Animal Models of Phenylketonuria: Pros and Cons.International journal of molecular sciences · 2025Review
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Rapid and definitive treatment of phenylketonuria in variant-humanized mice with corrective editing.Nature communications · 2023Article
- Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor.Science China. Life sciences · 2022Article
- A universal strategy for AAV delivery of base editors to correct genetic point mutations in neonatal PKU mice.Molecular therapy. Methods & clinical development · 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
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord.Frontiers in molecular neuroscience · 2021Review
- Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.Molecular therapy. Methods & clinical development · 2020Article
- 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
- Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).Scientific reports · 2019Article
- Treatment of a metabolic liver disease by in vivo genome base editing in adult mice.Nature medicine · 2018Article
- Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein.Molecular therapy. Nucleic acids · 2018Article
- Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter.Molecular therapy. Nucleic acids · 2017Article
- AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice.Molecular genetics and metabolism · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU) is an inborn error of metabolism caused by deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH) which leads to high blood phenylalanine (Phe) levels and consequent damage of the developing brain with severe mental retardation if left untreated in early infancy. The current dietary Phe restriction treatment has certain clinical limitations. To explore a long-term nondietary restriction treatment, a somatic gene transfer approach in a PKU mouse model (C57Bl/6-Pahenu2) was employed to examine its preclinical feasibility. A recombinant adeno-associated virus (rAAV) vector containing the murine Pah-cDNA was generated, pseudotyped with capsids from AAV serotype 8, and delivered into the liver of PKU mice via single intraportal or tail vein injections. The blood Phe concentrations decreased to normal levels (< or =100 microM or 1.7 mg/dl) 2 weeks after vector application, independent of the sex of the PKU animals and the route of application. In particular, the therapeutic long-term correction in females was also dramatic, which had previously been shown to be difficult to achieve. Therapeutic ranges of Phe were accompanied by the phenotypic reversion from brown to black hair. In treated mice, PAH enzyme activity in whole liver extracts reversed to normal and neither hepatic toxicity nor immunogenicity was observed. In contrast, a lentiviral vector expressing the murine Pah-cDNA, delivered via intraportal vein injection into PKU mice, did not result in therapeutic levels of blood Phe. This study demonstrates the complete correction of hyperphenylalaninemia in both males and females with a rAAV serotype 8 vector. More importantly, the feasibility of a single intravenous injection may pave the way to develop a clinical gene therapy procedure for PKU patients.
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