| Human alpha-iduronidase gene transfer mediated by adeno-associated virus types 1, 2, and 5 in the brain of nonhuman primates: vector diffusion and biodistribution. | |
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MedLine Citation:
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PMID: 19272011 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously demonstrated that delivery of a recombinant adeno-associated virus (rAAV) encoding human alpha-iduronidase (hIDUA) in the putamen and centrum semiovale was feasible and beneficial in a dog model of Hurler's syndrome. In the present study, we investigated the safety and vector diffusion profile of three rAAV serotypes (rAAV2/1, rAAV2/2, and rAAV2/5), encoding hIDUA in the central and peripheral nervous systems of nonhuman primates. Six macaques received the same vector dose injected into the right putamen and the homolateral internal capsule. Neurological examinations were done regularly and showed no detectable clinical consequence of the intracerebral injections. Because transgene IDUA was indistinguishable from endogenous enzymatic activity, we looked for vector diffusion by performing quantitative polymerase chain reaction on serial sections from the brain and spinal cord. We found that global diffusion throughout the brain was not significantly different between the three serotypes. However, rAAV2/1 and rAAV2/5 resulted in higher vector copy numbers per cell than did rAAV2/2, respectively, in the brain and the distal neuronal structures (spinal cord and peripheral nerves). |
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Authors:
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Carine Ciron; Arnaud Cressant; Françoise Roux; Sylvie Raoul; Yan Cherel; Philippe Hantraye; Nicole Déglon; Bertrand Schwartz; Martine Barkats; Jean-Michel Heard; Marc Tardieu; Philippe Moullier; Marie-Anne Colle |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human gene therapy Volume: 20 ISSN: 1557-7422 ISO Abbreviation: Hum. Gene Ther. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-02 Completed Date: 2009-07-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: United States |
Other Details:
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Languages: eng Pagination: 350-60 Citation Subset: IM |
Affiliation:
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INSERM U649, 44000 Nantes, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / metabolism* Cranial Nerves / metabolism Dependovirus / genetics* Diffusion Gene Transfer Techniques* Genetic Vectors / administration & dosage, pharmacokinetics* Genome, Viral Humans Iduronidase / genetics* Injections, Intraventricular Internal Capsule / metabolism Leukocytes, Mononuclear / metabolism Macaca / genetics* Organ Specificity Peripheral Nerves / metabolism Putamen / metabolism Spinal Cord / metabolism Tissue Distribution Transgenes Virion / genetics |
| Chemical | |
Reg. No./Substance:
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EC 3.2.1.76/Iduronidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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