ArticleJournal of inherited metabolic disease1998
Developing adenoviral-mediated in vivo gene therapy for ornithine transcarbamylase deficiency.
Article in Journal of inherited metabolic disease, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 43 citations in OpenAlex.
- Current Treatment Modalities for Urea Cycle Disorders.Paediatric drugs · 2025Review
- New Directions in Pulmonary Gene Therapy.Human gene therapy · 2020Review
- Review
- Gene therapy for metabolic disorders: an overview with a focus on urea cycle disorders.Journal of inherited metabolic disease · 2012Article
- Sustained correction of OTC deficiency in spf( ash) mice using optimized self-complementary AAV2/8 vectors.Gene therapy · 2012Article
- Human dendritic cells infected with an adenoviral vector suppress proliferation of autologous and allogeneic T cells.Immunology · 2008Article
- Helper-dependent adenoviral vectors in experimental gene therapy.Acta biochimica Polonica · 2005Review
- Localized adenovirus gene delivery using antiviral IgG complexation.Gene therapy · 2001Article
- In vivo detection of gene expression in liver by 31P nuclear magnetic resonance spectroscopy employing creatine kinase as a marker gene.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- Ornithine carbamoyltransferase deficiency.Archives of disease in childhood · 2001Review
- Review
- Efficient mitochondrial import of newly synthesized ornithine transcarbamylase (OTC) and correction of secondary metabolic alterations in spf(ash) mice following gene therapy of OTC deficiency.Molecular medicine (Cambridge, Mass.) · 1999Article
- In vivo measurement of ureagenesis with stable isotopes.Journal of inherited metabolic disease · 1998Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
There are a number of reasons for choosing ornithine transcarbamylase (OTC) deficiency as a candidate for gene therapy: the gene has been cloned; the disorder is relatively common; the current clinical outcome is poor; and there are authentic animal models. In considering the development of gene therapy for OTC deficiency, we focused on the use of in vivo gene therapy with an adenoviral vector. Using the partially OTC-deficient sparse fur mouse we found transduction and expression could be achieved using an intravenous infusion of a recombinant adenovirus containing the OTC cDNA. The results were transient as a result of immune activation in response to the vector and vector-transduced cells. By modifying the adenoviral construct, creating an E1 deletion-E2 temperature-sensitive mutation, we blunted the cytotoxic T lymphocyte immune response and achieved correction of biochemical abnormalities for 2-3 months. We also found that transduction and expression following gene transfer occurred sufficiently rapidly to protect against acute hyperammonaemia within 24 h. Subsequent preclinical studies in mice and non-human primates demonstrated that E1-E4-deleted vectors had a substantially improved safety profile and similar efficacy. With this evidence of efficacy and safety of adenoviral vectors, we are embarking on a phase I trial of intravascular gene transfer using an E1-E4-deleted vector in adults with partial OTC deficiency.
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Registered trials
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