MODELING OF HUMAN HBV INFECTION WITH A TRANSFECTED RAT HEPATOMA CELL LINE

这是与麻省理工学院石家和博士合作的项目 宾夕法尼亚大学生物化学和生物物理学教授Leo Lee博士 弗雷德里克癌症研究机构和Div.袁DeVires博士。 生物化学和生物物理学，食品和药物管理局。史医生患上了大鼠肝癌 转染人乙肝病毒的细胞株的建立 克隆了HBVDNA。这株细胞系Q7 21-乙肝病毒被提供给我们用于 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，它提供了理解 这种病毒的物种屏障存在于附着和/或 病毒对肝细胞的渗透。我们曾尝试将其用于 寻找乙肝病毒抑制药物的体外模型系统及探索 潜在的治疗方案。我们已经设计和合成了许多 未修饰或硫代化的反义寡核苷酸 形式。我们已经标准化了体外测试系统来测试这些 反义DNA。初步结果显示，大多数寡核苷酸 对细胞培养来说毒性太大，而且只有一种修饰形式 抑制效应。更多的药物将在此进行搜索和探索 系统。

This is a collaborative program with Dr. Chiaho Shih of Department 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 transfection 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.