Objective: To explore the inhibitory effect of triplex forming oligodeoxynucleotides(TFO) on replication of HBV and synthesis of antigen.
Methods: A 21 mer phosphorothioate triplex forming oligodeoxynucleotides (TFO21) directed at SP1 sites in HBV core promoter and a control of 21 mer phosphorothioate oligodeoxynucleotides (ODNcon) were synthesized. HepG 2.2.15 cells which can produce HBsAg, HBeAg, HBV DNA and HBV particle were treated with TFO21 and ODNcon. In HepG 2.2.15 cells treated with these oligodeoxynucleotides, the levels of HBsAg, HBeAg, and HBV DNA were examined by ELISA and dot hybridization method, respectively.
Results: The levels of HBsAg, HBeAg and HBV DNA in TFO21 group were lower than those in the bank control group. At concentration of 10 mumol/L, TFO21 inhibited synthesis of HBsAg and HBeAg by 57.5% and 77%. The inhibitory effect of TFO21 was dosage-dependent, and was related to time in which 2.2.15 cells were incubated with TFO21. No inhibition was observed in the ODNcon group. No toxicity was observed in the 2.2.15 cells treated with oligodeoxynucleotides.
Conclusion: These results indicate that TFO is a potent inhibitor for HBV replication and synthesis of antigen, and also suggest that TFO is a therapeutic potential for the treatment of patients infected with HBV.