Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus E1A Proteins / deficiency
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Adenovirus E1A Proteins / genetics
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Adenoviruses, Human / genetics*
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Adenoviruses, Human / isolation & purification
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Animals
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Bronchi / metabolism
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Bronchi / microbiology
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Bronchi / transplantation*
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Cell Differentiation
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Cystic Fibrosis Transmembrane Conductance Regulator
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Defective Viruses / genetics*
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Defective Viruses / isolation & purification
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Epithelium / metabolism
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Epithelium / microbiology
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Epithelium / transplantation
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Gene Expression
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Genetic Therapy / methods*
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Genetic Vectors*
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Humans
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Leg
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Male
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics*
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Mice
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Mice, Nude
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Rats
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Rats, Inbred F344
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Recombinant Fusion Proteins / biosynthesis
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Safety
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Trachea / transplantation
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Transfection*
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Transplantation, Heterologous*
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Transplantation, Heterotopic
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Viral Proteins / biosynthesis
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Viral Proteins / genetics
Substances
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Adenovirus E1A Proteins
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CFTR protein, human
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Membrane Proteins
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Recombinant Fusion Proteins
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Viral Proteins
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Cystic Fibrosis Transmembrane Conductance Regulator