Animal models of human diseases play a critical role in the development of new therapeutic modalities, such as gene therapy. Implementation of any human gene therapy protocol requires experimental evidence of efficacy as defined by the metabolic, pathologic, and/or clinical correction of the disease processes. In addition it is critical that a careful assessment of toxicity is performed in at least two species of animals, one of which is usually a non-human primate. Authentic animal models provide the only valid experimental setting in which to assess these parameters. In addition, the availability of animal models greatly simplifies the development of such therapies. The University of Pennsylvania provides an outstanding environment in which to utilize animal models for the development of gene therapies. The School of Veterinary Medicine is a world class program located on the medical center campus that has a long tradition for identifying and characterizing animal models of human diseases. The Animal Models core (AMC) builds on the strengths of existing programs to develop expertise, facilities, and resources necessary for basic develop of gene therapies and the rapid application of these technologies to the treatment of cystic fibrosis (CF) and genetic diseases. The following components of the AMC will be available to center participants: (1) Colonies of the mouse model for CF have been established at the University of Pennsylvania in collaboration with Dr. Richard Boucher from the University of North Carolina. The animals are currently being developed to enable expression of pathology in other tissues such as lung and liver. (2) We have developed an animal model for CF airway that is based on the growth of a human CF bronchial xenograft in a nu/nu mouse. The xenografts will be established by AMC core personnel in collaboration with Dr. J. Engelhardt, and will be provided to Center Participants when available. (3) Specialized biohazard operating room suites have been renovated at the University of Pennsylvania and the Wistar Institute for use by the IHGT. These facilities, along with support personnel, will be provided to center participants. (4) To facilitate the preclinical assessment of toxicity associated with proposed gene therapies of cystic fibrosis and genetic diseases, a specialized facility has been constructed to house up to 60 primates under biohazard containment conditions in accordance with Good Laboratory Practices. These facilities and the support staff will be available to Center Participants.
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