Dexamethasone enhancement of gene expression after direct hepatic DNA injection.
The critical physiological functions of the liver make hepatocytes important targets for therapeutic gene delivery. This study reports significant gene expression following direct injection of plasmid DNA into the livers of rats and cats. Transfection was characterized using luciferase and Lac Z expression from plasmids with the cytomegalovirus immediate early promoter/enhancer (CMV IE) or the Rous sarcoma virus long terminal repeat (RSV LTR). Dexamethasone treatment enhanced and prolonged transfected gene expression, possibly by activating gene expression. Southern analysis of total DNA extracted from liver at various times following injection detected persistent unintegrated plasmid DNA which maintained a prokaryotic methylation pattern. This study demonstrates the feasibility of direct DNA injection in the experimental analysis of hepatic gene expression in vivo.
Department of Medicine:Pathology, University of California, Davis 95616.
R W
RW
Malone
M A
MA
Hickman
K
K
Lehmann-Bruinsma
T R
TR
Sih
R
R
Walzem
D M
DM
Carlson
J S
JS
Powell
D000818:Animals; D001483:Base Sequence; D002415:Cats; D002478:Cells, Cultured; D004274:DNA, Recombinant; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007763:Lac Operon; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012091:Repetitive Sequences, Nucleic Acid
D004274:DNA, Recombinant; D003907:Dexamethasone; D008156:Luciferases