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Journal of Virology, May 2000, p. 4816-4823, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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, and
Fabio
Palombo*
IRBM P. Angeletti, Rome, Italy
Received 22 September 1999/Accepted 4 February 2000
The current therapy for hepatitis B and C is based on systemic
administration of recombinant human alpha interferon (r-hIFN-
). However, systemic delivery of r-hIFN-
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-
antiviral efficacy, we have explored the therapeutic potential of murine IFN-
2
(mIFN
2) selectively expressed in the liver. To this end, we have
developed a helper-dependent adenovirus vector (HD) containing the
mIFN-
2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-
2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in
the absence of detectable circulating mIFN-
2. 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-
2.
*
Corresponding author. Mailing address: IRBM P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia (Rome), Italy. Phone:
39-06-91093-234. Fax: 39-06-91093-225. E-mail:
palombo{at}irbm.it.
Journal of Virology, May 2000, p. 4816-4823, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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