[In vivo inhibition of hepatitis B virus replication and gene expression by targeted phosphorothioate modified antisense oligodeoxynucleotides].
OBJECTIVE
To investigate the antiviral effect of targeted antisense oligodeoxynucleotides (asODN) in HBV transgenic mice.


METHODS
asODN phosphorothioated (5'-CATGCCCCAAAGCCAC-3') targeted to HBV pre-C/C region was synthesized. Gal15-PLL was used as drugs carrier which targeted asODN to mice liver. Twelve mice with positive serum HBsAg, HBV-DNA were divided into the Gal15-PLL-asODN-treated group or the control group randomly. In Gal15-PLL- asODN-treated group, each mouse was injected i.v. asODN 15mug/g weighty/day via tail vein for 12 days successively; while in the control group, each mouse received the same volume normal saline by the same way.


RESULTS
In the Gal15-PLL- asODN-treated group, serum HBsAg decreased at the 6th day (P<0.05), and decreased significantly at the 12th day vs pretreatment (P<0.01). The serum HBV DNA of 4/6 mice became negative. Immunohistochemistry test showed lowered HBsAg, HBcAg content in the liver. In contrast, the control group showed no apparent changes.


CONCLUSIONS
Gal15-PLL-asODN targeted to pre-C/C region could inhibit HBV replication and gene expression.
Zhong
Sen
S
Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
Zheng
Su Jun
SJ
Chen
Feng
F
Wen
Shou Ming
SM
Wang
Sheng Qi
SQ
Zhang
Jian Jun
JJ
Deng
Chun Liang
CL
D000818:Animals; D004279:DNA, Viral / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides