RNA Interference inhibits HBV of different genotypes in Vitro and in Vivo

StephenW

http://www.biomedcentral.com/content/pdf/1471-2180-10-214.pdf
RNA Interference inhibits Hepatitis B Virus of different
genotypes in Vitro and in Vivo
Ya-Li Zhang 1, Tong Cheng 1,§, Yi-Jun Cai 1, Quan Yuan 1, Che Liu 1, Tao Zhang 1,
De-Zhen Xia 1, Rui-Yin Li 1, Lian-Wei Yang 1, Ying-Bin Wang 1, Anthony E. T. Yeo 1,
James. Wai-Kuo Shih 1, Jun Zhang 1, Ning-shao Xia 1
1 National Institute of Diagnostics and Vaccine Development in Infectious Diseases,
School of Life Science, Xiamen University, Xiamen, Fujian Province, China
§
Corresponding authors. Address: National Institute of Diagnostics and Vaccine
Development in Infectious Diseases, School of Life Science, Xiamen University,
Siming South Road No.422, Xiamen, Fujian Province 361005, People’s Republic of
China. Phone: +86-0592-2184113. Fax: +86-0592-2181258. Email:
[email protected]
Email addresses:
YLZ: [email protected]
TC: [email protected]
YJC: [email protected]
QY: [email protected]
CL: [email protected]
TZ: [email protected]
DZX: [email protected]
RYL: [email protected]
LWY: [email protected]
YBW: [email protected]
AEY: [email protected]
JWS: [email protected]
JZ: [email protected]
NSX: [email protected]
Abstract
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.



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