Zhong Sen, Zheng Su Jun, Chen Feng, Wen Shou Ming, Wang Sheng Qi, Zhang Jian Jun, Deng Chun Liang
Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
Zhonghua Gan Zang Bing Za Zhi. 2002 Aug;10(4):283-6.
To investigate the antiviral effect of targeted antisense oligodeoxynucleotides (asODN) in HBV transgenic mice.
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.
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.
Gal15-PLL-asODN targeted to pre-C/C region could inhibit HBV replication and gene expression.
研究靶向反义寡脱氧核苷酸（asODN）对乙肝病毒转基因小鼠的抗病毒作用。
合成针对乙肝病毒前C/C区的硫代磷酸化asODN（5'-CATGCCCCAAAGCCAC-3'）。使用Gal15-PLL作为药物载体，将asODN靶向至小鼠肝脏。将12只血清乙肝表面抗原（HBsAg）、乙肝病毒DNA（HBV-DNA）阳性的小鼠随机分为Gal15-PLL-asODN治疗组和对照组。在Gal15-PLL-asODN治疗组中，每只小鼠通过尾静脉连续12天每天注射15μg/g体重的asODN；而在对照组中，每只小鼠以相同方式接受相同体积的生理盐水。
在Gal15-PLL-asODN治疗组中，血清HBsAg在第6天下降（P<0.05），与治疗前相比，在第12天显著下降（P<0.01）。6只小鼠中有4只的血清HBV DNA转为阴性。免疫组织化学检测显示肝脏中HBsAg、乙肝核心抗原（HBcAg）含量降低。相比之下，对照组无明显变化。
靶向前C/C区的Gal15-PLL-asODN可抑制HBV复制和基因表达。
