Lentiviral gene transfer to the nonhuman primate brain.

Détails

ID Serval
serval:BIB_13F2D89184E3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lentiviral gene transfer to the nonhuman primate brain.
Périodique
Experimental neurology
Auteur(s)
Kordower J.H., Bloch J., Ma S.Y., Chu Y., Palfi S., Roitberg B.Z., Emborg M., Hantraye P., Déglon N., Aebischer P.
ISSN
0014-4886
Statut éditorial
Publié
Date de publication
1999
Peer-reviewed
Oui
Volume
160
Numéro
1
Pages
1-16
Langue
anglais
Notes
Publication types: Journal Article - Publication Status: ppublish
Résumé
Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.
Mots-clé
Animals, Brain, Caudate Nucleus, Feasibility Studies, Gene Therapy, Genes, Reporter, Genes, Synthetic, Genetic Vectors, Hepatitis B Virus, Woodchuck, Injections, Lac Operon, Lentivirus, Macaca mulatta, Male, Mice, Nerve Tissue Proteins, Parkinson Disease, Secondary, Phosphoglycerate Kinase, Promoter Regions, Genetic, Putamen, Recombinant Fusion Proteins, Stereotaxic Techniques, Substantia Nigra, beta-Galactosidase
Pubmed
Web of science
Création de la notice
06/02/2008 11:03
Dernière modification de la notice
20/08/2019 13:42
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