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

可复制的小鼠反转录病毒(RCR)可在某些 基因治疗产品制备中细胞系包装案例 为人类使用而产生的。因为与男性RCR相关的风险是 建议对RCR进行未知的严格测试，以排除可能的 产品受到污染。在之前的研究中，正常和 中度免疫抑制的猴子接种RCR指示的RAPI 病毒清除和无病理(Cornetta等人，1991)；然而，最近的 研究表明，RCR与淋巴瘤的发生有关 严重免疫抑制的恒河猴(Donahue等人，1992)。评估 关于RCR在人类中的潜在风险，我们承诺分析RCR的作用 在感染和淋巴肿大方面，使用猴子作为灵长类动物模型系统。 将RCR制剂接种给4只正常幼年恒河猴 研究正在进行中，以分析 使用每两周采集一次的血液样本检测猴子的传染性- 接种：对PBL进行病毒分离测试；获取血浆以用于 免疫印迹分析检测抗体；DNA是从猪的外周血淋巴细胞中提取的 用聚合酶链式反应分析病毒DNA。此外，临床血液学和血清 化学反应正在上演。

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.