The purpose of this study is to evaluate the safety and efficacy of gene therapy of cystic fibrosis with a replication deficient E1, E3 deleted adenovirus that directs expression of the normal CFTR mRNA and CFTR protein in mammalian cells. In phases I of this study, the virus, AV1CF2 will be administered to the upper (nasal) and lower (lobar bronchial) respiratory tract of patients with cystic fibrosis. This protocol is designed to demonstrate 1) the transfer of CFTR mRNA in vivo 2) the synthesis of CFTR protein and 3) the correction of epithelial cell cAMP dependent Cl permeability associated with cystic fibrosis. Potential toxic effects of AV1CF2 will be monitored measuring clinical, radiographic, physiologic and biochemical parameters. The """"""""pharmacokinetics"""""""" or longevity of expression of AV1CF2 will be determined. Systemic and local immunologic consequences of AV1CF2 infection, the time of viral survival, and the potential for recombination or complementation of the virus to produce a replicating virus will be monitored in assessing the safety of the AV1CF2 recombinant virus. In phase 2 of the project, the safety and efficacy of repeated administration and then whole lung administered to the lungs of children with minimal lung disease and longer term follow-up will be initiated. It is hoped that these studies will demonstrate the biologic expression in vivo and the clinical safety and efficacy of the AV1CF2 vector. This would support the long term goal CFTR gene transfer that will lead to prevention of the abnormalities that cause pulmonary disease in children with cystic fibrosis.
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