title: Gene therapy of the central nervous system: general considerations on viral vectors for gene transfer into the brain.
abstract: The last decade has nourished strong doubts on the beneficial prospects of gene therapy for curing fatal diseases. However, this climate of reservation is currently being transcended by the publication of several successful clinical protocols, restoring confidence in the appropriateness of therapeutic gene transfer. A strong sign of this present enthusiasm for gene therapy by clinicians and industrials is the market approval of the therapeutic viral vector Glybera, the first commercial product in Europe of this class of drug. This new field of medicine is particularly attractive when considering therapies for a number of neurological disorders, most of which are desperately waiting for a satisfactory treatment. The central nervous system is indeed a very compliant organ where gene transfer can be stable and successful if provided through an appropriate strategy. The purpose of this review is to present the characteristics of the most efficient virus-derived vectors used by researchers and clinicians to genetically modify particular cell types or whole regions of the brain. In addition, we discuss major issues regarding side effects, such as genotoxicity and immune response associated to the use of these vectors.
authors.affiliation: CEA, DSV, I(2)BM, Molecular Imaging Research Center (MIRCen) and CNRS, CEA URA 2210, 18, route du Panorama, 92265 Fontenay-aux-Roses, France.
authors.forename: C
authors.initials: C
authors.lastname: Serguera
authors.affiliation: CEA, DSV, I(2)BM, Molecular Imaging Research Center (MIRCen) and CNRS, CEA URA 2210, 18, route du Panorama, 92265 Fontenay-aux-Roses, France. Electronic address: alexis.bemelmans@cea.fr.
authors.forename: A-P
authors.initials: AP
authors.lastname: Bemelmans
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000145:classification / Q000627:therapeutic use*; D006801:Humans; D016086:Lentivirus / Q000235:genetics
keywords: Adeno-associated virus vectors; Adenoviral vectors; Central nervous system; Gene therapy; Genotoxicity; Génotoxicité; Immune response; Lentiviral vectors; Réponse immunitaire; Système nerveux central; Thérapie génique; Vecteurs adénoviraux; Vecteurs lentiviraux; Vecteurs viraux adéno-associés