肝细胞靶向性脂质体介导的硫代磷酸反义寡核苷酸在体内外抑制乙型肝炎病毒的研究  

In vitro and in vivo inhibition of HBV by phosphorothioate antisense oligonucleotides via a hepatocyte-targeted liposome

作　　者：文立民[1] 任中原[2] 

机构地区：[1]军事医学科学院生物工程研究所,北京100071 [2]天津医科大学微生物学教研室,天津300070

出　　处：《生物技术通讯》1998年第2期91-94,共4页Letters in Biotechnology

摘　　要：在体外细胞培养系统和裸鼠动物体内,观察了人肝细胞靶向性脂质体介导的部分硫代型和全部硫代型反义寡核苷酸对乙型肝炎病毒的抑制作用。结果显示,针对HBVe基因翻译起始区的18聚体的硫代磷酸反义寡核苷酸在体内、外对HBV DNA、HBV mRNA及HBsAg、HBeAg均有不同程度的抑制作用。研究说明,反义寡核苷酸是抗HBV有效的基因治疗候选药物。We developed a hepatocyte-targeted DNA carrier system which consisting of liposome and a desialated gly-coprotein (ASOR) since there are abundant and unique ASOR receptors on the surface of hepatocytes. In HBV DNA transfected human hepatoma cell line 2. 2. 15 in vitro culture system, we studied the inhibition of HBV by 18 mer phosphorothioate antisense oligodeoxynucleotides (asODN) which targeting HBV e gene mRNA translating origin via hepatocyte-targeted liposome. The in vitro results showed 1 μmol asODNs could inhibit 88% HBsAg and 43% HBeAg maximally. Southern and Northern dot blot suggested it also could inhibit the replication of HBV DNA and the transcription of HBV mRNA markedly. Inoculating 3× 107 2. 2. 15 cells per mouse subcutaneously into 5-6 weeks old Bal b/c nude mice could extablish animal model producing HBV markers. In this HBV in vivo system, asODNs were injected around the tumor via hepatocyte-targeted liposome with a dose of 80 μg per gram body weight and 2 days later the amounts of HBV antigens and HBV DNA in the sera of treated nude mice were markedly lower than that in controls. The asODNs we designed seemed to be an effective anti-HBV gene therapeutic drugs.

关 键 词：反义寡核苷酸 乙型肝炎病毒 靶向性脂质体 人肝癌细胞 抑制作用 

分 类 号：R346[医药卫生—基础医学]