STUDY OF A MURINE RETROVIRUS FROM A PACKAGING CELL LINE USED IN GENE THERAPY

用于基因治疗的来自包装细胞系的鼠逆转录病毒的研究

• 批准号: 3770323
• 负责人: A S KHAN
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3770323
• 关键词: Macaca mulatta; Retroviridae; artificial immunosuppression; blood chemistry; disease /disorder model; disease /disorder proneness /risk; gene therapy; juvenile animal; lymphoma; neoplasm /cancer genetics; polymerase chain reaction; tissue /cell culture; viral carcinogenesis; viral rescue; virus DNA; virus diseases; virus genetics; virus replication; western blottings

Replication-competent murine retroviruses (RCRs) can be generated in some cases from packaging cell lines used in preparation of gene therapy product generated for human use. Since the risk associated with RCR in man is unknown, rigorous testing for RCRs is recommended to exclude possible contamination of the product. Previous studies in which normal and moderately immunosuppressed monkeys were inoculated with RCR indicated rapi virus clearance and no pathology (Cornetta et al, 1991); however, a recent study has shown RCR to be associated with development of lymphomas in severely immunosuppressed rhesus monkeys (Donahue et al, 1992). To assess the potential risk of RCRs in man, we undertook to analyze the role of RCRs in infection and lymphomagenesis using monkeys as a primate model system. Four normal juvenile rhesus monkeys were inoculated with a RCR preparation obtained from Genetic Therapy Inc. Studies are in progress to analyze the monkeys for infectivity using blood samples obtained every two weeks post- inoculation: PBLs are tested for virus isolation; plasma is obtained for antibody detection by Western blot analysis; DNAs are prepared from PBLs fo analysis of viral DNA by PCR. In addition clinical hematology and serum chemistry is being performed.

复制能力小鼠逆转录病毒（RCRs）可以在一些