Abstract:Objective In order to evaluate the potential efficacy of siRNA compounds for hepatitis B virus (HBV) infected population in China, a representative cell model for HBV in China was constructed. Methods The Chinese HBV reference genome was constructed by selected 1 416 B2 HBV genome sequences and 1 636 C2 HBV genome sequences that were epidemic in China. And on this basis, the cell model of the representative HBV in China was constructed. The expression of cellular HBV DNA and cellular supernatants hepatitis B surface antigen (HBsAg) and Hepatitis e antigen (HBeAg) was used to evaluate whether the system was successfully constructed. The siRNA compounds evaluated by this system were further tested in HBV transgenic mice. Results HBV DNA, HBsAg and HBeAg were all expressed normally in the two cell models, and the expression values of B2 type were 50 585 copies/μl, 0.55 PEIU/mL and 55.88 IU/mL. And the expression values of type C2 were 45 302 copies/μl, 35.31 PEIU/mL and 56.9 IU/mL, respectively. Compound BPR2030, which was evaluated by the B2 and C2 cell model, was injected subcutaneously into HBV transgenic mice with a single dose of 3mg/kg. The maximum expression of HBV DNA, HBsAg and HBeAg in mice serum was decreased by 1.82 (log10 IU/mL), 2.55 (log10 IU/mL) and 0.95 (log10 PEIU/mL) compared with the baseline, and the activity was significantly better than the positive control 7-35 days after dosing (P<0.05). Conclusion The Chinese representative HBV expressing cells are successfully constructed, and the siRNA evaluated by the cell model shown high activity against HBV virus in HBV transgenic mice, indicating that the cell model is stable and reliable, and favors more targeted development of gene-based drugs suitable for HBV patients in China