DIRECT GENE-TRANSFER OF HUMAN CFTR INTO HUMAN BRONCHIAL EPITHELIA OF XENOGRAFTS WITH E1-DELETED ADENOVIRUSES

We describe the use of a human bronchial xenograft model for studying the efficiency and biology of in vivo gene transfer into human bronchi al epithelia with recombinant E1 deleted adenoviruses. All cell types in the surface epithelium except basal cells efficiently expressed the adenoviral transduced recombinant genes, lacZ and CFTR, for 3-5 weeks . Stable transgene expression was associated with high level expressio n of the early adenoviral gene, E2a, in a subset of transgene expressi ng cells and virtually undetectable expression of the late adenoviral genes encoding the structural proteins, hexon and fiber. These studies begin to address important issues that relate to safety and in vivo e fficacy of recombinant adenoviruses for gene delivery into the human a irway.