title: Gene therapeutic approach for inhibiting hepatitis C virus replication using a recombinant protein that controls interferon expression.
abstract: The hepatitis C virus (HCV) is a continuing threat to public health. The systemic administration of interferon alpha with ribavirin is the only currently approved treatment. However, this treatment is associated with a wide spectrum of systemic side effects that limits its effectiveness; thus, there is an urgent need for new treatment modalities. In this study, we describe a novel anti-HCV strategy employing a recombinant transcription factor that we have engineered in such a way that NS3/4a viral protease controls its intracellular localization, thereby restoring interferon secretion specifically in cells infected with HCV. Proof-of-concept experiments validated the strategy, showing that the recombinant transcription factor was triggered to stimulate interferon promoter by NS3/4A and remained inactive in cells without NS3/4a. Using an adenovirus-associated viral vector delivery system, we found that the recombinant transcription factor inhibited HCV replication effectively in vitro in cultured cells.
authors.affiliation: Department of Microbiology, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul 138-736, South Korea. chjoo@amc.seoul.kr
authors.forename: Chul Hyun
authors.initials: CH
authors.lastname: Joo
authors.forename: Uk
authors.initials: U
authors.lastname: Lee
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Nam
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.forename: Young Keol
authors.initials: YK
authors.lastname: Cho
authors.forename: Yoo Kyum
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000628:therapy* / Q000821:virology; D006801:Humans; D015151:Immunoblotting; D007372:Interferons / Q000378:metabolism*; D008954:Models, Biological; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D007372:Interferons