Objective: To evaluate the activity in vivo of 3 phosphorothioate antisense oligonucleotides, HCV363, HCV279 and HCV349 using nude mice xenograft models based on the establishment of HCV 5' NCR transgenic cellular model (HepG2.9706).
Methods: Female BALB/C nude mice, aged 4 to 6 weeks and weighing around 20g, were implanted s.c. with 100mul (106 cells) of the HepG2.9706 cells suspension in the lower-back region. In approximate 1 weeks, the animals were randomly grouped and intraperitoneally administrated the antisense drugs at 10 mg/kg body weight.
Results: HCV363, HCV279 and HCV349 had obvious sequence-specific inhibitory effects on luciferase expression controlled by HCV 5' NCR in xenograft cells with the inhibitory rates of 80.4%, 78.6% and 47.9%, respectively. The effects of three different concentrations (5, 10, 20 mg/kg body weight) of HCV363 indicated that HCV363 increased the inhibitory activities on luciferase expression following the concentration raise and its inhibitory rate was up to 82.7%.
Conclusions: This study suggests that antisense oligonucleotides may provide a novel therapeutic approach to the treatment of HCV infection.