CORE--ANIMAL MODEL FACILITY

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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.