In vivo inhibition of hepatitis B virus replication and gene expression by targeted phosphorothioate modified antisense oligodeoxynucleotides / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the antiviral effect of targeted antisense oligodeoxynucleotides (asODN) in HBV transgenic mice.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Gal15-PLL-asODN targeted to pre-C/C region could inhibit HBV replication and gene expression.</p>