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

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 v...

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Detalles Bibliográficos
Autores: Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91, Ochoa, L. (Laura)|||/items/86ab2c6d-1b27-4130-8f8b-89170ec22907, Crettaz, J. (Julien)|||/items/684f8e38-df97-41b5-b96c-cc35728ac1cb, Rotellar-Sastre, F. (Fernando)|||/items/833cb788-f4b9-404d-a18b-ae1c84369b51, Vales, A. (África)|||/items/f3b4e7dd-a2f9-4e77-9562-32b512a3772a, Martinez-Anso, E. (Eduardo)|||/items/5dfb13aa-fbc9-49ee-9fe5-746b904397bd, Zaratiegui, M. (Mikel)|||/items/d6ca7a55-d31b-4b01-a044-4c922e6ba8b0, Ruiz, J. (Juan)|||/items/e71ee758-aef7-4ed6-b282-e483e9d9ba8e, González-Aseguinolaza, G. (Gloria)|||/items/cb28732d-02bf-4339-ab60-ff738ee191ac, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Tipo de recurso: artículo
Fecha de publicación:2005
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/20332
Acceso en línea:https://hdl.handle.net/10171/20332
Access Level:acceso abierto
Palabra clave:Dependovirus
Hepatitis B/therapy
Interferon-alpha/genetics
Marmota/virology
Descripción
Sumario: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.

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