Gene therapeutic approach for inhibiting hepatitis C virus replication using a recombinant protein that controls interferon expression.
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.
Joo
Chul Hyun
CH
Department of Microbiology, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul 138-736, South Korea. chjoo@amc.seoul.kr
Lee
Uk
U
Nam
Young Ran
YR
Jung
Jae U
JU
Lee
Heuiran
H
Cho
Young Keol
YK
Kim
Yoo Kyum
YK
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
D011994:Recombinant Proteins; D007372:Interferons