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

Abstract:

:The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-alpha). However, systemic delivery of r-hIFN-alpha 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-alpha antiviral efficacy, we have explored the therapeutic potential of murine IFN-alpha2 (mIFNalpha2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-alpha2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-alpha2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-alpha2. 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-alpha2.

journal_name

J Virol

journal_title

Journal of virology

authors

Aurisicchio L,Delmastro P,Salucci V,Paz OG,Rovere P,Ciliberto G,La Monica N,Palombo F

doi

10.1128/jvi.74.10.4816-4823.2000

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

4816-23

issue

10

eissn

0022-538X

issn

1098-5514

journal_volume

74

pub_type

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