CREATION OF IMMORTALIZED CHIMP AND BABOON HEPATOCYTE CELL LINES

永生化黑猩猩和狒狒肝细胞系的创建

• 批准号: 7716129
• 负责人: Robert E LANFORD
• 金额: $ 0.2万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716129
• 关键词: Adult; Adverse effects; Cell Line; Cirrhosis; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Gene Transduction Agent; Goals; Grant; Hepatitis C; Hepatitis C virus; Hepatocyte; Institution; Liver diseases; Malignant neoplasm of liver; Modeling; Oncogenes; Pan Genus; Pan troglodytes; Papio; Pegylated Interferon Alfa; Population; Primary carcinoma of the liver cells; Rate; Research; Research Personnel; Resources; Ribavirin; Risk; Series; Source; Subfamily lentivirinae; United States National Institutes of Health; Virus Replication; Week; cancer type; liver transplantation; nonhuman primate; novel; programs; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Worldwide, approximately 170 million people are chronically infected with hepatitis C virus (HCV) which frequently progresses to serious liver disease, including cirrhosis and liver cancer or hepatocellular carcinoma (HCC). Approximately 4% of the adult population is HCV positive. The current therapy involves the combination of pegylated interferon-alpha and ribavirin, is very difficult to tolerate due to severe side effects, requires 48 weeks of treatment, and has less than 50% response rate. HCV infection is the leading cause for liver transplantation in the US and liver cancer due to HCV infection is one of the most rapidly increasing types of cancer in the US. The long term goal of this program is to develop a new non-human primate model for HCV infection, preferably the baboon, for studies exploring the mechanism of hepatitis C virus associated disease and liver cancer. A series of conceptual and technical breakthroughs have occurred in the past two years which suggest that the adaptation of HCV to a non-human primate other than the chimpanzee is feasible. This is a high risk, high payoff proposal. The short term goal during the first year is to develop novel chimpanzee and baboon liver cell lines using lentivirus gene therapy vectors to deliver multiple oncogenes to primary hepatocytes. The cell lines will then be used to force the adaptation of HCV for replication in these cell lines and presumably non-human primates other than the chimpanzee.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 全世界约有1.7亿人慢性感染丙型肝炎病毒（HCV），经常进展为严重的肝病，包括肝硬化和肝癌或肝细胞癌（HCC）。大约4%的成年人为丙型肝炎病毒阳性。目前的治疗涉及聚乙二醇化干扰素-α和利巴韦林的组合，由于严重的副作用而非常难以耐受，需要48周的治疗，并且具有小于50%的响应率。在美国，HCV感染是肝移植的主要原因，并且由于HCV感染引起的肝癌是美国增长最快的癌症类型之一。 该计划的长期目标是开发一种新的非人灵长类HCV感染模型，最好是狒狒，用于探索丙型肝炎病毒相关疾病和肝癌机制的研究。在过去的两年中，出现了一系列概念和技术突破，这表明HCV适应非人灵长类动物而不是黑猩猩是可行的。这是一个高风险，高回报的提议。第一年的短期目标是开发新的黑猩猩和狒狒肝细胞系，使用慢病毒基因治疗载体将多种癌基因传递到原代肝细胞。然后，这些细胞系将用于迫使HCV适应这些细胞系和可能的非人灵长类动物（黑猩猩除外）中的复制。