CHARACTERIZATION & SAFETY TESTING OF CLINICAL RETROVIRUS

该合同项目的主要目标是提供临床分级 将用于靶向体细胞人的逆转录病毒载体上清液 基因治疗试验中的体外细胞。这将涉及到生产 逆转录病毒产生系的主细胞库的超低温保存 这种库的存储，在某些情况下，生产工作细胞库和 超低温保存储存库，生产多升 临床级逆转录病毒上清液的量及其保存 超低温保存。这一目标的一个组成部分是实现 对产生逆转录病毒的细胞系进行各种安全测试 载体上清液、逆转录病毒上清液本身以及对人类的影响 在培养中用这种逆转录病毒载体转导的细胞。是这样的 安全测试将包括但不限于验证 生产线的源头，检测多种类型的污染 病原体，以及复制能力强的逆转录病毒的检测。 此类安全测试的执行方式将验证 逆转录病毒上清液和转导细胞产品用于 临床试验符合监管机构制定的安全标准 美国食品和药物管理局的要求。其中一个 这种基因治疗试验的目标疾病是遗传免疫系统。 缺乏称为慢性肉芽肿病(CGD)。在临床上 CGD试验来自CGD患者的血液干细胞将被 在培养中暴露于由该病毒提供的临床级逆转录病毒 合同。干细胞的实际培养和转导不是 这一合同项目，但对转导干细胞的安全测试 产品是合同项目的目标。

The main objective of this contract project is to provide clinical grade retrovirus vector supernatant that will be used for targeting somatic human cells ex vivo in trials of gene therapy. This will involve the production of a master cell banks of the retrovirus producer lines, cryopreservation storage of such banks, in some cases production of working cell banks and cryopreservation storage of such banks, production of multi-liter quantities of clinical grade retrovirus supernatant and its storage by cryopreservation. An integral part of this objective is performance of a variety of safety testing on the cell lines which produce the retrovirus vector supernatant, the retrovirus supernatant itself, and on the human cells that are transduced with this retrovirus vector in culture. Such safety testing would include, but is not restricted to verification of the source of producer lines, detection of many types of contaminating pathogenic organisms, and detection of replication competent retrovirus. Such safety testing will be performed in a manner which will verify that the retrovirus supernatant and transduced cell products to be used in the clinical trial conform to the safety standards set by regulatory requirements of the United States Food and Drug Administration. One of the target diseases for such gene therapy trials is the inherited immune system deficiency known as chronic granulomatous disease (CGD). In the clinical trial for CGD the blood stem cells derived from patients with CGD will be exposed in culture to the clinical grade retrovirus provided by this contract. The actual culture and transduction of stem cells is not part of this contract project, but the safety testing of the transduced stem cell product is an objective of the contract project.