Nature Genetics
4, 27 - 34 (1993)
doi:10.1038/ng0593-27
Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1−deleted adenovirusesJohn F. Engelhardt1, 4, Yiping Yang1, 4, Leslie D. Stratford-Perricaudet2, Edward D. Allen1, Karen Kozarsky1,4, Michel Perricaudet2, James R. Yankaskas3
& James M. Wilson1, 4
1Departments of Internal Medicine and Biological Chemistry University of Michigan, Ann Arbor, Michigan 48109-0650, USA
2CNRS UA 1301 Institut Gustave Roussy, Villejuif 94805, Cedex, France
3Division of Pulmonary Diseases, The University of North Carolina Chapel Hill, North Carolina, 27599-7020, USA
4Institute for Human Gene Therapy, The University of Pennsylvania, Wistar Institute, 36th & Spruce Streets, Philadelphia, Pennsylvania, 19104-4268, USA Correspondence should be addressed to J.M.W. We describe the use of a human bronchial xenograft model for studying the efficiency and biology of in vivo gene transfer into human bronchial 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 expression of the early adenoviral gene, E2a, in a subset of transgene expressing 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 efficacy of recombinant adenoviruses for gene delivery into the human airway.
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