| Upon infection with hepatitis B virus (HBV) the result will be either a chronic infection or clearance of the virus. For the chronic carriers of HBV, therapy is primarily limited to nucleoside analogs, which inhibits viral replication and prevents production of progeny virus, however the nucleoside analogs have little affect on the reservoir of the virus in the nucleus, the covalently closed circular DNA (cccDNA). Our lab previously designed zinc finger proteins (ZFPs) to target sequences within the duck hepatitis B virus (DHBV) and HBV cccDNAs to inihibit hepadnaviral replication. This is a novel approach to treatment of HBV infection because the reservoir of the virus is directly targeted. The DHBV-specific ZFPs have been shown to inhibit DHBV replication in tissue culture. I have assessed the ability of HBV-specific ZFPs, delivered by lentiviral vectors, to inhibit HBV transcription in two HBV-infected human hepatoma cell lines. The currently designed ZFPs failed to suppress HBV replication. |
