Document Detail

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.
MedLine Citation:
PMID:  19272011     Owner:  NLM     Status:  MEDLINE    
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).
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human gene therapy     Volume:  20     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2009-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  350-60     Citation Subset:  IM    
INSERM U649, 44000 Nantes, France.
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MeSH Terms
Brain / metabolism*
Cranial Nerves / metabolism
Dependovirus / genetics*
Gene Transfer Techniques*
Genetic Vectors / administration & dosage,  pharmacokinetics*
Genome, Viral
Iduronidase / genetics*
Injections, Intraventricular
Internal Capsule / metabolism
Leukocytes, Mononuclear / metabolism
Macaca / genetics*
Organ Specificity
Peripheral Nerves / metabolism
Putamen / metabolism
Spinal Cord / metabolism
Tissue Distribution
Virion / genetics
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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