Liver-specific alpha 2 interferon gene expression results in protection from induced hepatitis

Luigi Aurisicchio, Paola Delmastro, Valentina Salucci, Odalys Gonzalez Paz, Patrizia Rovere, Gennaro Ciliberto, Nicola La Monica, Fabio Palombo

Research output: Contribution to journalArticlepeer-review

Abstract

The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-α). However, systemic delivery of r-hIFN-α is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-α antiviral efficacy, we have explored the therapeutic potential of murine IFN-α2 (mIFNα2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-α2 gene under the control of the liver- specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-α2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-α2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-α2.

Original languageEnglish
Pages (from-to)4816-4823
Number of pages8
JournalJournal of Virology
Volume74
Issue number10
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Immunology

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