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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 the inhibition of gene replication and expression of hepatitis B virus by liposome-mediated antisense oligonucleotide in vitro. Methods A total of 2251 cells were used as target cells. Phosphorothioate antisense Oligonucleotides (PS-ASON) were designed and synthesized based on the HBVS and PreC gene translation initiation regions. Liposomes were used to promote transfection. Measured by radioimmunoassay (RLA) of hepatitis B virus HBsAg, HBeAg content. Results Liposome-mediated PS-ASON specifically inhibited the production of 90% HBsAg and 92% HBeAg at a concentration of 1 μmol / L, while no cytotoxic effect was observed. The antiviral effect of liposome-mediated antisense oligonucleotide (ASON) was significantly higher than that of ASON alone (P <0.01). Conclusion Liposome-mediated ASON is a promising anti-HBV drug.