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

这是与施嘉和博士合作项目的延续 的Dept。宾夕法尼亚大学生物化学和生物物理学博士。 弗雷德里克癌症研究机构的李利奥和 Div.生物化学和生物物理学，FDA。 施博士培育了一种老鼠 肝癌细胞系，其通过以下方式产生人B肝炎病毒（HBV）： 用克隆的HBV DNA输血。 提供了该细胞系Q7 21-HBV 我们的合作研究项目。 因为这是第一次 HBV可以在非人类细胞系中繁殖，它提供了 了解到这种病毒的物种障碍在于 病毒附着和/或穿透肝细胞。 我们有 尝试使用该体外模型系统来寻找HBV抑制剂， 药物和探索潜在的治疗方案。 我们已经设计并 合成了许多反义寡脱氧核苷酸， 硫代磷酸酯化形式。 我们已经标准化了体外测定系统， 检测这些反义DNA 初步结果显示， 寡脱氧核苷酸对细胞培养物毒性太大， 修饰形式具有抑制作用。 其他药物将 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 propogated 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-sence oligodeoxynucleotides in either unmodified or phosphorothiolated form. We have standardized an in vitro assay system to test these anti-sence 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.