Therapeutic approach to hepatitis C using single-chain antibody and DNA gene transfer

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A cDNA for single-chain antibody (sFv) against hepatitis B virus core protein (HBc), 1C9, was isolated. We also cloned a cDNA for control sFv (γ9) that could not react HBc. HB611 cells that carry three copies of HBV-DNA and produce HBV particles were transfected with 1C9 or γ9 and we established the HB611 cells that stably express 1C9 or γ9, respectively. We found no difference in production of each HBV transcript and protein between 1C9-expressing HB611 and γ9-expressing ones. However, expression of HBV replicative intermediate was inhibited in 1C9-expressing HB611 compared with γ9-expressing ones. These results suggested that sFv against HBc might inhibit the packaging of pregenome RNA into HBc particles. Thus sFv against viral capsid protein was shown to be useful for inhibition of encapsidation of viral genome and sFv against hepatitis C virus core protein may be a candidate for therapeutic application of hepatitis C.