CORE--ANIMAL MODEL FACILITY

任何人类基因治疗方案的实施都需要实验性的 根据代谢、病理和/或临床定义的疗效证据 纠正疾病的过程。除了药效，媒介 用于管理遗传信息必须经过严格的检测 安全。动物模型在新技术的发展中起着关键作用 重组腺病毒，如目前正在开发的 囊性纤维化的基因治疗。真正的动物模型提供了 用于评估安全参数的唯一有效的实验设置。 必须对至少两种物种进行仔细的毒性评估 其中一种是非人灵长类动物。 宾夕法尼亚大学在 利用动物模型来开发成功的基因 治疗方案。动物模型核心(AMC)建立在 现有计划的优势，包括大学实验室 资源和Wistar动物基金，以发展专业知识， 开发基因疗法所需的设施和资源 以及这些技术在囊性疾病治疗中的快速应用 纤维化(CF)。AMC的以下组件将用于 对实验策略的测试： (1)建立了棉鼠(Sigmodon Hispidus)群体 在宾夕法尼亚大学。棉鼠的组织更多 比其他物种更容易感染腺病毒，并且 在涉及重组基因的毒理学研究中尤其有用 腺病毒。这些动物目前被用来使 肺、肝、胰腺等组织的病理学评估。 (2)促进对与以下物质相关的毒性进行临床前评估 囊性纤维化和遗传性疾病的基因治疗建议 专门的设施，能够容纳多达60只灵长类动物 符合GOOD实验室的生物危害遏制条件 练习。这些设施和支持人员将可用于 适当的参与者。 (3)专门的生物危害手术室套房已在 宾夕法尼亚大学和维斯塔尔研究所供 需要动物模型来测试基因治疗的研究人员 治疗慢性萎缩性胃炎的策略。

Implementation of any human gene therapy protocol requires experimental evidence of efficacy as defined by metabolic, pathologic, and/or clinical correction of the disease processes. In addition to efficacy, vectors used in administering genetic information must be rigorously tested for safety. Animal models play a critical role in the development of new recombinant adenoviruses, such as those currently under development for the gene therapy of cystic fibrosis. Authentic animal models provide the only valid experimental setting in which to assess safety parameters. Careful assessment of toxicity must be performed in at least two species of animals, one of which is a non-human primate. The University of Pennsylvania provides an outstanding environment in which to utilize animal models for the development of a successful gene therapy protocols. The Animal Models Core (AMC) has built on the strengths of existing programs, including the University Laboratory Resources and the Wistar Animal Facility, to develop expertise, facilities, and resources necessary for the development of gene therapies and the rapid application of these techniques to the treatment of cystic fibrosis (CF). The following components of the AMC will be available for testing of experimental strategies: (1) Colonies of the Cotton rat (Sigmodon hispidus) have been established at the University of Pennsylvania. Tissues of the Cotton rat are more susceptible to adenoviral infection than other species, and are especially useful in toxicology studies involving recombinant adenoviruses. These animals are currently being used to enable evaluation of pathology in tissues such as lung, liver, and pancreas. (2) To facilitate the preclinical assessment of toxicity associated with proposed gene therapies of cystic fibrosis and genetic diseases, a specialized facility, which is capable of housing up to 60 primates under biohazard containment conditions in accordance with Good Laboratory Practices. These facilities and support staff will be available to appropriate participants. (3) Specialized biohazard operating room suites have been renovated at the University of Pennsylvania and the Wistar Institute for use by investigators who require animal models in which to test gene therapy strategies for the treatment of CF.