A POTENTIAL THERAPEUTIC APPLICATION OF HAIRPIN RIBOZYMES - IN-VITRO AND IN-VIVO STUDIES OF GENE-THERAPY FOR HEPATITIS-C VIRUS-INFECTION

Two effective ribozymes (CR2 and CR4) that target HCV RNA 5 UTR and ca psid gene regions were generated. Ribozyme cleavage was demonstrated i n vitro, which can be enhanced by facilitator RNA molecules. In tissue culture cells, these two ribozymes can inhibit the expression of a co transfected reporter gene containing HCV RNA target sequences. Further more, transduction of human hepatoma cells, HepG2, with retroviral vec tors carrying CR2 or CR4 ribozymes enabled the cells to resist the inf ection by retroviral particles containing HCV target sequences. These results represent the first positive step towards the application of h airpin ribozymes in gene therapy for the treatment of HCV infection.