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 Viroljournal_title
Journal of virologyauthors
Aurisicchio L,Delmastro P,Salucci V,Paz OG,Rovere P,Ciliberto G,La Monica N,Palombo Fdoi
10.1128/jvi.74.10.4816-4823.2000subject
Has Abstractpub_date
2000-05-01 00:00:00pages
4816-23issue
10eissn
0022-538Xissn
1098-5514journal_volume
74pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2007-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1979-05-01 00:00:00