Published on: 2010-08-10
Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) offers a new tool with potential therapeutic applications for HBV.
Given the high heterogeneity of HBV strains and the sensitivity of siRNA to the changes of sequences, finding potent siRNA inhibitors against the conservative site on HBV genome is essential to ensure the therapeutic application.
Results: Forty short hairpin RNA (shRNA) expression plasmids were constructed targeting conserved regions among 9 HBV genotypes. HBV 1.3-fold genome plasmids with various genotypes were co-transfected with shRNA plasmids to Huh7 cells or to mice.
The levels of various viral proteins were examined to assess anti-HBV efficacy of siRNA. Four shRNA plasmids (B245, B376, B1581 and B1789 ) were found to be able to potently inhibit HBV surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression of HBV genotypes A, B, C, D and I (a newly identified genotype ) both in Huh7 cells and in mice.
No unusual cytotoxicity or off-target effects were noted.
Conclusions: Such siRNA suggest an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising an advance in treatment of HBV.
Author: Ya-Li ZhangTong ChengYi-Jun CaiQuan YuanChe LiuTao ZhangDe-Zhen XiaRui-Ying LiLian-Wei YangYing-Bin WangAnthony YeoJames ShihJun ZhangNing-Shao Xia
Credits/Source: BMC Microbiology 2010, 10:214