PHASE I TRIAL OF INTRAMUSCULAR INJECTION OF A RECOMBINANT ADENO-ASSOCIATED VIRUS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A recombinant virus vector constructed from adeno associated virus (AAV) that has been altered to carry the human alpha 1-antitrypsin (hAAT) gene expressed from a hybrid chicken beta actin promoter with a cytomegalovirus enhancer has been developed. The construct has been shown to initiate the production of hAAT in animal models closely matching the proposed human trial. The proposed clinical trial is an open label, phase I study administering rAAV2-CB-hAAT gene vector intramuscularly to AAT deficient human subjects where gene expression can be measured directly in blood samples, to assess safety. Safety parameters will be measurement of changes, in serum chemistries and hematology, urinalysis, pulmonary function testing, semen assay for vector genomes, immunologic response to AAT, and AAV, as well as reported subject history of any symptoms.