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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Anticuerpos monoclonales > DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista >

IFN-alpha gene therapy for woodchuck hepatitis with adeno-associated virus: differences in duration of gene expression and antiviral activity using intraportal or intramuscular routes
Authors: Berraondo, P. (Pedro)
Ochoa, L. (Laura)
Crettaz, J. (Julien)
Rotellar, F. (Fernando)
Vales, A. (África)
Martinez-Anso, E. (Eduardo)
Zaratiegui, M. (Mikel)
Ruiz, J. (Juan)
Gonzalez-Aseguinolaza, G. (Gloria)
Prieto, J. (Jesús)
Keywords: Dependovirus
Hepatitis B/therapy
Interferon-alpha/genetics
Marmota/virology
Issue Date: 2005
Publisher: Nature Publishing Group
Publisher version: http://dx.doi.org/10.1016/j.ymthe.2005.02.017
ISSN: 1525-0016
Citation: Berraondo P, Ochoa L, Crettaz J, Rotellar F, Vales A, Martinez-Anso E, et al. IFN-alpha gene therapy for woodchuck hepatitis with adeno-associated virus: differences in duration of gene expression and antiviral activity using intraportal or intramuscular routes. Mol Ther 2005 Jul;12(1):68-76.
Abstract
Gene delivery of IFN-alpha to the liver may represent an interesting strategy to maximize its antiviral efficacy and reduce side effects. We used a recombinant adeno-associated virus (AAV) encoding woodchuck IFN-alpha (AAV-IFN) to treat animals with chronic woodchuck hepatitis virus infection. The vector was given by intraportal or intramuscular route. Long-term transgene expression was detected after intraportal administration of an AAV encoding luciferase. In contrast, in the majority of the animals that received AAV-IFN through the portal vein, the expression of IFN-alpha was transient (30-40 days) and was associated with a significant but transient decrease in viral load. One animal, in which hepatic production of IFN-alpha persisted at high levels, died because of bone marrow toxicity. The disappearance of IFN-alpha expression correlated with the disappearance of AAV genomes from the liver. Intramuscular administration of AAV-IFN resulted in prolonged but fluctuating expression of the cytokine with no significant antiviral effect. In summary, this report shows that long-term expression of IFN-alpha in muscle is feasible but higher interferon levels might be needed to control viral replication. On the other hand, IFN-alpha gene delivery to the liver using an AAV vector induces a significant but transient antiviral effect in the woodchuck model.
Permanent link: http://hdl.handle.net/10171/20332
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Terapia génica hepatitis virales - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - Medicina - Cirugía General - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista

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