Recombinant AAV-mediated gene delivery to the central nervous system.

Détails

ID Serval
serval:BIB_7C425707DAAD
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Recombinant AAV-mediated gene delivery to the central nervous system.
Périodique
Journal of Gene Medicine
Auteur(s)
Tenenbaum L., Chtarto A., Lehtonen E., Velu T., Brotchi J., Levivier M.
ISSN
1099-498X (Print)
ISSN-L
1099-498X
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
6
Numéro
Suppl. 1
Pages
S212-S222
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
Various regions of the brain have been successfully transduced by recombinant adeno-associated virus (rAAV) vectors with no detected toxicity. When using the cytomegalovirus immediate early (CMV) promoter, a gradual decline in the number of transduced cells has been described. In contrast, the use of cellular promoters such as the neuron-specific enolase promoter or hybrid promoters such as the chicken beta-actin/CMV promoter resulted in sustained transgene expression. The cellular tropism of rAAV-mediated gene transfer in the central nervous system (CNS) varies depending on the serotype used. Serotype 2 vectors preferentially transduce neurons whereas rAAV5 and rAAV1 transduce both neurons and glial cells. Recombinant AAV4-mediated gene transfer was inefficient in neurons and glial cells of the striatum (the only structure tested so far) but efficient in ependymal cells. No inflammatory response has been described following rAAV2 administration to the brain. In contrast, antibodies to AAV2 capsid and transgene product were elicited but no reduction of transgene expression was observed and readministration of vector without loss of efficiency was possible from 3 months after the first injection. Based on the success of pioneer work performed with marker genes, various strategies for therapeutic gene delivery were designed. These include enzyme replacement in lysosomal storage diseases, Canavan disease and Parkinson's disease; delivery of neuroprotective factors in Parkinson's disease, Huntington disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemia and spinal cord injury; as well as modulation of neurotransmission in epilepsy and Parkinson's disease. Several of these strategies have demonstrated promising results in relevant animal models. However, their implementation in the clinics will probably require a tight regulation and a specific targeting of therapeutic gene expression which still demands further developments of the vectors.
Mots-clé
Animals, Brain/metabolism, Dependovirus, Enzymes/genetics, Enzymes/metabolism, Genetic Engineering, Genetic Vectors, Nervous System Diseases/drug therapy, Transduction, Genetic, Transgenes
Pubmed
Web of science
Création de la notice
20/01/2008 18:35
Dernière modification de la notice
03/03/2018 18:37
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