Abstract
The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, flt-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.
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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Adenoviridae / genetics
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Animals
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Cell Line
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Endothelial Growth Factors / genetics
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Endothelium / metabolism
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Endothelium, Vascular / metabolism
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Gene Transfer Techniques*
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Genetic Therapy / methods*
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Genetic Vectors
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Immunohistochemistry
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Liver / metabolism
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Luciferases / metabolism
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Lung / metabolism
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Lymphokines / genetics
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Male
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Mice
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Peptidyl-Dipeptidase A / genetics
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Peptidyl-Dipeptidase A / metabolism
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Promoter Regions, Genetic
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Rats
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Rats, Sprague-Dawley
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Tissue Distribution
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Transcription, Genetic*
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Transduction, Genetic*
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Transgenes*
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Lymphokines
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Luciferases
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Peptidyl-Dipeptidase A