Recombinant adeno-associated virus expressing a modified transcription factor triggered by the hepatitis C viral protease NS3/4a.

Abstract

Many viruses, including hepatitis C virus (HCV), are major threats to public health, but few treatment options are available. Systemic administration of a combination of interferon-a and ribavirin is the only approved treatment for HCV. However, half of all patients are not cured by such treatment and a wide spectrum of systemic side-effects limits its effectiveness. I developed a gene therapy approach with three goals: 1) the restoration of local interferon secretion in cells infected with HCV, 2) no secretion of interferon in normal cells not infected with the virus, and 3) suppression of the emergence of resistant viral strains. A recombinant transcription factor was constructed, the intracellular localization of which is controlled by a viral protease to stimulate focal interferon secretion at sites of infection. A recombinant adenovirus associated virus expressing the transcription factor based on the described strategy inhibited HCV replication effectively in a HCV in vitro culture system.