ArticleHuman gene therapy2010
Comparison of adeno-associated virus pseudotype 1, 2, and 8 vectors administered by intramuscular injection in the treatment of murine phenylketonuria.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Live long and active: Polypeptide-mediated assembly of antibody variable fragments.Advanced drug delivery reviews · 2020Pooled it
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Clinical, genetic, and experimental research of hyperphenylalaninemia.Frontiers in genetics · 2022Review
- A noncoding RNA modulator potentiates phenylalanine metabolism in mice.Science (New York, N.Y.) · 2021Article
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- Study of the l-Phenylalanine Ammonia-Lyase Penetration Kinetics and the Efficacy of Phenylalanine Catabolism Correction Using In Vitro Model Systems.Pharmaceutics · 2021Article
- Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase.Molecular therapy. Methods & clinical development · 2020Article
- A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.Molecular genetics and metabolism · 2020Article
- Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia.International journal of molecular sciences · 2020Review
- State-of-the-Art 2019 on Gene Therapy for Phenylketonuria.Human gene therapy · 2019Review
- Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice.Journal of inherited metabolic disease · 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
- Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.PloS one · 2017Article
- Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders.Methods in molecular biology (Clifton, N.J.) · 2016Review
- New Strategies for the Treatment of Phenylketonuria (PKU).Metabolites · 2014Review
- Treatment of phenylketonuria using minicircle-based naked-DNA gene transfer to murine liver.Hepatology (Baltimore, Md.) · 2014Article
- Phenylketonuria: translating research into novel therapies.Translational pediatrics · 2014Review
- Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy.Scientific reports · 2013Article
- Clinical therapeutics for phenylketonuria.Drug delivery and translational research · 2012Article
- AAV-mediated gene targeting is significantly enhanced by transient inhibition of nonhomologous end joining or the proteasome in vivo.Human gene therapy · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Phenylketonuria (PKU) is caused by hepatic phenylalanine hydroxylase (PAH) deficiency and is associated with systemic accumulation of phenylalanine (Phe). Previously we demonstrated correction of murine PKU after intravenous injection of a recombinant type 2 adeno-associated viral vector pseudotyped with type 8 capsid (rAAV2/8), which successfully directed hepatic transduction and Pah gene expression. Here, we report that liver PAH activity and phenylalanine clearance were also restored in PAH-deficient mice after simple intramuscular injection of either AAV2 pseudotype 1 (rAAV2/1) or rAAV2/8 vectors. Serotype 2 AAV vector (rAAV2/2) was also investigated, but long-term phenylalanine clearance has been observed only for pseudotypes 1 and 8. Therapeutic correction was shown in both male and female mice, albeit more effectively in males, in which correction lasted for the entire period of the experiment (>1 year). Although phenylalanine levels began to rise in female mice at about 8-10 months after rAAV2/8 injection they remained only mildly hyperphenylalaninemic thereafter and subsequent supplementation with synthetic tetrahydrobiopterin resulted in a transient decrease in blood phenylalanine. Alternatively, subsequent administration of a second vector with a different AAV pseudotype to avoid immunity against the previously administrated vector was also successful for long-term treatment of female PKU mice. Overall, this relatively less invasive gene transfer approach completes our previous studies and allows comparison of complementary strategies in the development of efficient PKU gene therapy protocols.
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.