In vivo inhibition of hepatitis B virus replication and gene expression by targeted phosphorothioate modified antisense oligodeoxynucleotides.
- Author:
Sen ZHONG
1
;
Su Jun ZHENG
;
Feng CHEN
;
Shou Ming WEN
;
Sheng Qi WANG
;
Jian Jun ZHANG
;
Chun Liang DENG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; DNA, Viral; blood; Gene Expression; drug effects; Hepatitis B Surface Antigens; blood; Hepatitis B virus; drug effects; genetics; physiology; Mice; Mice, Transgenic; Oligodeoxyribonucleotides, Antisense; pharmacology; Thionucleotides; pharmacology; Virus Replication; drug effects
- From: Chinese Journal of Hepatology 2002;10(4):283-286
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the antiviral effect of targeted antisense oligodeoxynucleotides (asODN) in HBV transgenic mice.
METHODSasODN 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.
RESULTSIn 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.
CONCLUSIONSGal15-PLL-asODN targeted to pre-C/C region could inhibit HBV replication and gene expression.
