RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.
BACKGROUND
Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.


RESULTS
Forty short hairpin RNA (shRNA) expression plasmids were constructed to target conserved regions among nine HBV genotypes. HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with shRNA plasmids into either Huh7 cells or mice. The levels of various viral markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376, B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA, surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in mice. No unusual cytotoxicity or off-target effects were noted.


CONCLUSIONS
Such siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising advances in the treatment of HBV.
Zhang
Ya-Li
YL
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, Fujian Province, China.
Cheng
Tong
T
Cai
Yi-Jun
YJ
Yuan
Quan
Q
Liu
Che
C
Zhang
Tao
T
Xia
De-Zhen
DZ
Li
Rui-Yin
RY
Yang
Lian-Wei
LW
Wang
Ying-Bin
YB
Yeo
Anthony E T
AE
Shih
James Wai-Kuo
JW
Zhang
Jun
J
Xia
Ning-Shao
NS
D000818:Animals; D002460:Cell Line; D015316:Genetic Therapy; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics / Q000628:therapy / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D034741:RNA, Small Interfering; D014764:Viral Proteins