CORE--VECTOR PRODUCTION

核心——矢量制作

• 批准号: 6564370
• 负责人: KENNETH B TAYLOR
• 金额: $ 16.54万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564370
• 关键词: Adenoviridae; biomedical facility; cystic fibrosis; plasmids; technology /technique development; transfection /expression vector

Description: (Taken directly from the application) The Vector Production Core is intended to provide batch synthesis of adenoviral and plasmid DNA vectors for preclinical studies of gene transfer. We have identified a substantial need for large scale preparation of these vectors on our campus. We also plan development of improved techniques to minimize replication competent adenovirus (RCA) from batch preparations, and to improve plasmid yield. The principal role of the Vector Production Core Facility will be to assist with the transition between early laboratory proof-of-concept type studies and the scale-up production that becomes crucial in order to support preclinical (predominantly animal) gene therapy trials. The amounts and quality of preclinical grade vector needed for studies of pigs or non-human primates, or even for detailed studies in mice, rats, or rabbits are often well beyond the capabilities of an individual laboratory attempting to validate a particular construct. A Vector Production Core at our center is, therefore, requested on the following basis. First, a number of UAB faculty interested in cystic fibrosis or other gene-transfer experiments have indicated a need for the large-scale production of adenovirus or plasmid batch preparations. Second, a standardized format of preparative and large-scale production will facilitate the reproducibility and consistency of the preparations. Third, issues not normally managed in a single investigator?s laboratory can be best addressed in a centralized facility, such as the presence of replication competent adenovirus (RCA), or optimization of plasmid DNA yields. Finally, although not produced under formal, good manufacturing practice (GMP) conditions, the documentation and record keeping in the facility may help track any variability in the responses observed with different vector preparations and may also help optimize future vector reparations. Moreover, the good laboratory practice (GLP) conditions used in the facility will make vectors produced in Core B useful and relevant with regards to development of human clinical trials of gene therapy.

描述：(直接取自应用程序) 载体生产核心旨在提供腺病毒的批量合成 以及用于基因转移的临床前研究的质粒DNA载体。我们有 确定了大规模制备这些载体的实质性需求 我们的校园。我们还计划开发改进的技术，以尽量减少 从批量制备的增殖型腺病毒(RCA)，并改进 质粒产量。 病媒生产核心基金的主要作用将是协助 随着早期实验室概念验证型研究和 为了支持临床前阶段，扩大生产变得至关重要 (主要是动物)基因治疗试验。数量和质量 猪或非人灵长类动物研究所需的临床前等级矢量，或 即使是在小鼠、大鼠或兔子身上进行详细研究，也往往远远超出 单个实验室尝试验证特定 建造。因此，我们中心的矢量生产核心被要求在 以下是依据。首先，UAB的一些教职员工对囊肿症感兴趣 纤维化或其他基因转移实验表明，有必要对 大规模生产腺病毒或质粒批次制剂。第二，一个 标准化的备战形式和规模化生产将为 制剂的重复性和一致性。第三，问题不是 通常由一名调查员管理？S实验室最适合在 一个集中的设施，如有复制能力的存在 腺病毒(RCA)，或优化质粒DNA产量。最后，尽管不是 在正式的、良好的制造规范(GMP)条件下生产， 设施中的文件和记录保存可能有助于跟踪任何变异性 在用不同载体制剂观察到的反应中，也可能有助于 优化未来的矢量修复。此外，良好的实验室实践 (GLP)设施中使用的条件将使在核心B产生的载体 对人类临床试验的发展有用和相关 基因疗法。