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。 除功效外， 用于管理遗传信息的药物必须经过严格的测试， 安全为代价的 动物模型在开发新的 重组腺病毒，例如目前正在开发的用于 囊性纤维化的基因治疗 真实的动物模型提供了 评估安全性参数的唯一有效实验设置。 必须对至少两个物种进行仔细的毒性评估 其中一种是非人类灵长类动物。 宾夕法尼亚大学提供了一个出色的环境， 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动物设施，以发展专业知识， 发展基因疗法所需的设施和资源 以及这些技术在治疗囊性 纤维化（CF）。 AMC的以下组件将可用于 测试实验策略： (1)已建立棉鼠（Sigmodon hispidus）的群体 在宾夕法尼亚大学。 棉鼠的组织 比其他物种更易受腺病毒感染， 尤其可用于涉及重组的毒理学研究， 腺病毒。 这些动物目前被用来 组织如肺、肝和胰腺的病理学评价。 (2)为了便于临床前评估与下列药物相关的毒性： 囊性纤维化和遗传性疾病的基因疗法， 专门的设施，能够容纳多达60只灵长类动物， 符合药物非临床研究质量管理规范的生物危害控制条件 实践 这些设施和支持人员将提供给 合适的参与者。 (3)专门的生物危害手术室套房已翻新， 宾夕法尼亚大学和Wistar研究所， 需要动物模型来测试基因治疗的研究者 CF的治疗策略。

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.