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
| Autor: | 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), González-Aseguinolaza, G. (Gloria), Prieto, J. (Jesús) |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: | |
| Zdroj: | Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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