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Développement de nouvelles approches antivirales du virus de l'hépatite C basées sur l'utilisation d'interférons alpha variants et d'antisens de type Peptide Nucleic Acids.

Abstract : Infection by hepatitis C virus (HCV) remains a major cause of cirrhosis and hepatocellular carcinoma. Current treatments are successful in about 55% of the cases. Development of new antiviral strategies thus remains a priority. In this global context, we have evaluated new interferon-alpha variants in a subgenomic HCV replicon system. We could identified a variant, GEA007.1 which exhibits a more potent inhibitory activity towards HCV compared to currently used IFN alpha-2b associated with an higher signal transduction efficacy. We have also evaluated an antisense approach with Peptide Nucleic Acids (PNA) molecules and showed its efficacy to inhibit HCV in vitro translation by blocking the internal ribosome entry site (IRES), in a much specific and efficient way compared with first generation antisense molecules. Such a strategy is justified by the high degree of conservation of the target which could be useful with the future use of anti HCV protease and anti HCV polymerase and the risk that resistance against treatment may appear. Taken together, our results suggest that improving actual combination therapy is possible and that new therapeutical approaches work.
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https://tel.archives-ouvertes.fr/tel-00136018
Contributor : Amaury Martin <>
Submitted on : Saturday, March 10, 2007 - 10:03:16 PM
Last modification on : Thursday, November 21, 2019 - 2:22:21 AM
Long-term archiving on: : Wednesday, March 29, 2017 - 1:33:23 PM

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  • HAL Id : tel-00136018, version 1

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Amaury Martin. Développement de nouvelles approches antivirales du virus de l'hépatite C basées sur l'utilisation d'interférons alpha variants et d'antisens de type Peptide Nucleic Acids.. Immunologie. Université Claude Bernard - Lyon I, 2007. Français. ⟨tel-00136018⟩

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