[Inhibition of hepatitis B virus (HBV) replication using antisense LNA targeting to both S and C genes in HBV].
OBJECTIVE
To investigate the inhibitory effect on HBV replication of antisense locked nucleic acid (LNA) targeting to both S and C genes in HBV transgenic mice.


METHODS
Thirty HBV transgenic mice were randomly divided into five groups (n = 6): glucose control group were treated with 5% glucose solution, liposome control group were treated with liposome alone, S group were treated with LNA targeting to S gene, C group were treated with LNA targeting to C gene, and dual-target group were treated with LNA targeting to both S and C genes. Antisense LNA was injected into mice via the tail vein. Serum HBsAg was quantified by TRFIA. Serum HBV DNA was quantified by real-time PCR. The expression of HBV C-mRNA in the liver was detected by RT-PCR. The expression of HBsAg and HBcAg in the liver was detected by immunohistochemistry. Serum ALB, ALT, BUN and CR were measured using an automatic biochemical analyzer. The effects of antisense LNA on mouse organs were investigated by HE staining.


RESULTS
5 days after LNA injection, serum HBsAg levels in the dual-target group were reduced by 72.8%, and serum HBV DNA levels were decreased by 52.9%. These values were significantly higher than those in the control groups (all P < 0.05). No significant differences were noted in serum ALB, ALT, BUN and CR between the experiment groups and the control groups (all P > 0.05). The expression levels of HBsAg and HBcAg in the liver of dual-target group were significantly lower than those in the control groups. No significant histopathological abnormality was found in liver and kidney tissues in all groups.


CONCLUSIONS
Antisense LNA targeting to both S and C genes can significantly inhibit HBV replication in transgenic mice.
Deng
Yi-bin
YB
Center for Medical Laboratory Science, the Affiliated Hospital of Youjiang Medical College for Nationalities, Baisei 533000, Guangxi Zhuang Autonomous Region, China.
Nong
Le-gen
LG
Huang
Wei
W
Pang
Guo-gang
GG
Wang
Yan-fei
YF
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011897:Random Allocation; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D008081:Liposomes; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid