Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter

Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recomb...

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Bibliographic Details
Published in:The Journal of surgical research 1997-10, Vol.72 (2), p.155-161
Main Authors: Dematteo, R.P., McClane, S.J., Fisher, K., Yeh, H., Chu, G., Burke, C., Raper, S.E.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - ultrastructure
Amylases - analysis
Amylases - genetics
Animals
Base Sequence
Biological and medical sciences
Blotting, Southern
Dexamethasone - pharmacology
DNA - analysis
DNA - chemistry
DNA - genetics
Gene Expression Regulation, Viral
Genetic Therapy
Genetic Vectors
HeLa Cells
Humans
Insulin - pharmacology
Lac Operon - genetics
Medical sciences
Mice
Mice, Inbred C57BL
Miscellaneous
Models, Genetic
Pancreas - enzymology
Pancreas - metabolism
Pharmacology. Drug treatments
Promoter Regions, Genetic - genetics
Recombination, Genetic
Transcription, Genetic - genetics
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Summary:Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express thelacZmarker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.
ISSN:0022-4804
1095-8673
DOI:10.1006/jsre.1997.5096