脂质体介导反义寡核苷酸体外抗乙型肝炎病毒作用的研究

Inhibition of hepatitis B virus replication and expression in vitro by Liposome-mediated antisense phosphorothioate oligonucleotides

目的 研究脂质体介导的反义寡核苷酸在体外对乙型肝炎病毒基因复制和表达的抑制。方法 以 2 2 1 5细胞为靶细胞 ,针对HBVS基因和PreC基因翻译起始区设计合成了 1 6聚硫代反义寡核苷酸 (PhosphorothioateAntisenseOligonucleotides,PS -ASON) ,脂质体促进转染。用放射免疫测定法 (RLA)测乙型肝炎病毒HBsAg、HBeAg含量。结果 脂质体介导PS -ASON在浓度 1 μmol/L时特异性抑制 90 %HBsAg和 92 %HBeAg的产生 ,同时未见对细胞的毒性作用。脂质体介导反义寡核苷酸 (AntisenseOligonucleotides,ASON)的抗病毒作用显著高于单独用ASON (P <0 0 1 )。结论 脂质体介导的ASON是一种很有潜力的抗HBV药物。

Objective To study antiviral effect of Lihposome-mediated antisense oligonucleotides COS-ASIN.Methods in vitro.The 2 2 15 cells were chosen as an in vitro cell assay system and a 16-mer phosphorothioate antisense oligonucleotides (PS-ASON) was synthesized and Liposome-mediated against surface and preC region of HBV gene.Results Liposome-mediated PS-ASON could inhibit specifically 90% of HBsAg and 92% of HBeAg produced at the concentration of 1μmol/L,The Liposome-mediated ASON had greater antiviral inhibitory than non-liposome-mediated ASON effect.Condusions Liposome-mediated ASON is a potential anti-HBV drug