Recombinant AAV viral vectors serotype 1, 2, and 5 mediate differential gene transfer efficiency in rat striatal fetal grafts.

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State: Public
Version: Final published version
Serval ID
serval:BIB_6AA2382470F2
Type
Article: article from journal or magazin.
Collection
Publications
Title
Recombinant AAV viral vectors serotype 1, 2, and 5 mediate differential gene transfer efficiency in rat striatal fetal grafts.
Journal
Cell Transplantation
Author(s)
Lubansu A., Abeloos L., Bockstael O., Lehtonen E., Blum D., Brotchi J., Levivier M., Tenenbaum L.
ISSN
0963-6897[print], 0963-6897[linking]
Publication state
Published
Issued date
2008
Volume
16
Number
10
Pages
1013-1020
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Intrastriatal grafts of fetal ganglionic eminences (GE) can reverse symptoms of striatal lesions in animal models of Huntington's disease. On the other hand, neurotrophic factors have been shown to protect host striatal neurons from ongoing degeneration. Neurotrophic gene transfer into GE prior to grafting could combine the benefits of striatal neuron replacement and in situ delivery of neurotrophic factors. Here we evaluate the potency of recombinant adeno-associated viruses (rAAV) as vectors for gene delivery into rat embryonic (E15) GE using the eGFP reporter gene under the control of the strong cytomegalovirus (CMV) promoter. We observed a very efficient expression of the eGFP reporter gene in organotypic cultures of GE infected with rAAV serotype 1 from 4 days until at least 4 weeks postinfection. In contrast, transduction was low and absent when using serotype 2 and serotype 5 rAAV, respectively. Two months after transplantation of rAAV2/1-infected embryonic GE in adult rat striatum, more than 20% of grafted cells expressed eGFP. The majority of transduced cells in the graft were neurons as indicated by colabeling of GFP-immunoreactive cells with the NeuN marker. Our study suggests that GE transduced by rAAV-serotype 1 vectors could be an interesting tool to mediate efficient expression of a gene coding a neurotrophic factor in Huntington's disease.
Keywords
Animals, Brain Tissue Transplantation/methods, Cell Survival, Cell Transplantation, Corpus Striatum/cytology, Cytomegalovirus/genetics, Dependovirus/genetics, Fetus, Gene Transfer Techniques, Genetic Vectors, Green Fluorescent Proteins/biosynthesis, Green Fluorescent Proteins/genetics, Neurons/cytology, Organ Culture Techniques, Promoter Regions, Genetic, Rats, Rats, Wistar
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14/03/2011 14:09
Last modification date
20/08/2019 14:25
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