Engineering tissue-specific expression of a recombinant adenovirus: selective transgene transcription in the pancreas using the amylase promoter.
Recombinant adenovirus accomplishes highly efficient gene transfer in 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 the lacZ marker 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.
Dematteo
R P
RP
Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
McClane
S J
SJ
Fisher
K
K
Yeh
H
H
Chu
G
G
Burke
C
C
Raper
S E
SE
D000256:Adenoviridae / Q000235:genetics* / Q000648:ultrastructure; D000681:Amylases / Q000032:analysis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011995:Recombination, Genetic; D014158:Transcription, Genetic / Q000235:genetics*
D007328:Insulin; D003907:Dexamethasone; D004247:DNA; D000681:Amylases