MODELING OF HUMAN HBV INFECTION WITH A TRANSFUSION RAT HEPATITIS CELL LINE

这是与施家和博士合作项目的延续 所属部门宾夕法尼亚大学生物化学和生物物理学系。 弗雷德里克癌症研究机构的利奥·李和袁德维斯博士 迪夫。生物化学和生物物理学，食品和药物管理局。施博士研制出一种大鼠 产生人乙肝病毒的肝癌细胞株 用克隆的HBVDNA输血。提供了该细胞系Q7 21-乙肝病毒 提供给我们的合作研究项目。因为这是第一次 乙肝病毒可以在非人类细胞系中繁殖，这提供了 了解到这种病毒的物种障碍在于 病毒附着和/或穿透到肝细胞。我们有 尝试使用该体外模型系统来寻找乙肝病毒抑制物 并探索潜在的治疗方案。我们设计并制作了 合成了许多反义寡核苷酸 硫代磷酸盐。我们已经标准化了体外测试系统，以 测试这些反义DNA。初步结果显示，大多数 寡核苷酸对细胞培养毒性太大，只有一种 修饰形式具有抑制作用。其他药物将是 在这个系统中搜索和探索。

This is a continuation of the collaborative program with Dr. Chiaho Shih of Dept. of Biochemistry and Biophysics, University of Pennsylvania, Dr. Leo Lee of the Frederick Cancer Research Facility and Dr. Yuan Devires of Div. Biochemistry and Biophysics, FDA. Dr. Shih has developed a rat hepatoma cell line which produced human hepatitis B virus (HBV) by transfusion with cloned HBV DNA. This cell line, Q7 21-HBV, was provided to us for collaborative research projects. Since this was the first time that HBV could be propagated in a non-human cell line, it provided the understanding that the species barrier for this virus lay on the attachment and/or penetration of the virus to hepatocyte. We have attempted to use this in vitro model system to search for HBV inhibitory drugs and to explore the potential treatment scheme. We have designed and synthesized many anti-sense oligodeoxynucleotides in either unmodified or phosphorothiolated form. We have standardized an in vitro assay system to test these anti-sense DNA. Preliminary results showed that most oligodeoxynucleotides are too toxic to cell culture and only one of the modified forms possessed inhibitory effect. Additional drugs will be searched and explored in this system.