ArticleMolecular therapy : the journal of the American Society of Gene Therapy2005
Low therapeutic threshold for hepatocyte replacement in murine phenylketonuria.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- Amelioration of the neurological phenotype in PKU mouse model emphasizes the potential of base editing for metabolic diseases.Molecular therapy. Advances · 2026Article
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- Article
- Base editing strategies forMolecular therapy. Nucleic acids · 2025Article
- Therapeutic liver cell transplantation to treat murine PKU.Journal of inherited metabolic disease · 2024Article
- Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.Nature biotechnology · 2024Article
- 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
- Clinical, genetic, and experimental research of hyperphenylalaninemia.Frontiers in genetics · 2022Review
- Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes.Science translational medicine · 2021Article
- Development of a porcine model of phenylketonuria with a humanized R408W mutation for gene editing.PloS one · 2021Article
- A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.Molecular genetics and metabolism · 2020Article
- AAV-Mediated CRISPR/Cas9 Gene Editing in Murine Phenylketonuria.Molecular therapy. Methods & clinical development · 2020Article
- The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.Expert opinion on orphan drugs · 2020Article
- Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses.Nature biomedical engineering · 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
- Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.Molecular genetics and metabolism · 2018Article
- Host conditioning and rejection monitoring in hepatocyte transplantation in humans.Journal of hepatology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phenylalanine homeostasis in mammals is primarily controlled by liver phenylalanine hydroxylase (PAH) activity. Inherited PAH deficiency (phenylketonuria or PKU) leads to hyperphenylalaninemia in both mice and humans. A low level of residual liver PAH activity ensures near-normal dietary protein tolerance with normal serum phenylalanine level, but the precise threshold for normal phenylalanine clearance is unknown. We employed hepatocyte transplantation under selective growth conditions to investigate the minimal number of PAH-expressing hepatocytes necessary to prevent hyperphenylalaninemia in mice. Serum phenylalanine levels remained normal in mice exhibiting nearly complete liver repopulation with PAH-deficient hepatocytes (<5% residual wild-type liver PAH activity). Conversely, transplantation of PAH-positive hepatocytes into PAH-deficient Pah(enu2) mice, a model of human PKU, yielded a significant decrease in serum phenylalanine (<700 muM) when liver repopulation exceeded approximately 5%. These data suggest that restoration of phenylalanine homeostasis requires PAH activity in only a minority of hepatocytes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.