title: RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.
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.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, Fujian Province, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Cai
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Che
authors.initials: C
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: De-Zhen
authors.initials: DZ
authors.lastname: Xia
authors.forename: Rui-Yin
authors.initials: RY
authors.lastname: Li
authors.forename: Lian-Wei
authors.initials: LW
authors.lastname: Yang
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Wang
authors.forename: Anthony E T
authors.initials: AE
authors.lastname: Yeo
authors.forename: James Wai-Kuo
authors.initials: JW
authors.lastname: Shih
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
mesh_terms: 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
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins