The Immunology/Pathology of The University of Florida Gene Therapy enter has been formed to assist investigators participating in gene therapy projects aimed at reversing and/or preventing phenyhlketonuria (PKU), alpha-1-anti-trypsin (AAT) deficiency, disorders of glycogen storage, and pilot projects related to diseases of the liver. Specifically, the Core will support these investigations by performing immunological and pathological analyses that characterize the host's immune system and cell/tissue response to agents proposed for or actively used in clinical trials based on gene therapy. This goal will be accomplished by performance of two specific aims: 1) Determine the immunogenicity of recombinant adeno-associated virus (rAAV) transgene products and capsid protein administered to animals in studies investigating long-term therapeutic gene transfer and expression; 2) Determine the tissue compartment of engraftment in host tissue, both with respect to site(s) of engraftment and toxicity of endogenous host tissues. Such studies Are vital in order to evaluate whether engraftment and toxicity to endogenous host tissues. Such studies are vital in order to evaluate whether methods for limiting/eliminating immune responses against vector capsid proteins and transgene products or directing engraftment/reducing cellular toxicity (were they identified) require development. Specific examples of vector based systems to which these services will be provided/applied include the rAAV, rAAV-green fluorescent protein, rAAV-acid alpha- glucosidase, and adenovirus infection based systems. In addition to providing a critical element for assurance of therapeutic safety, the Immunology/Pathology Core should provide information that will enhance the feasibility and efficacy of gene delivery trials.
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