Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats.
BACKGROUND
The purpose of this study was to achieve stomach-selective gene transfer in rats by our simple and novel administration method, which is gastric serosal surface instillation of naked plasmid DNA (pDNA).


METHODS
Naked pDNA encoding firefly luciferase as a reporter gene was instilled onto the gastric serosal surface in male Wistar rats. As controls, we performed intraperitoneal, intragastric and intravenous administration of naked pDNA. At appropriate time intervals, we measured luciferase activities in the stomach and other tissues.


RESULTS
Gene expression in the stomach 6 h after gastric serosal surface instillation of naked pDNA (5 microg) was significantly higher than that after using other administration methods. The present study is the first report on stomach-selective gene transfer following instillation of naked pDNA onto the gastric serosal surface in rats. Also, the gene expression level in the stomach 6 h after gastric serosal surface instillation of naked pDNA was markedly higher than that in other tissues. In a dose-dependent study, the gene expression level was saturated over 5 microg. Gene expression in the stomach was detected 3 h after gastric serosal surface instillation of naked pDNA. The gene expression level peaked 12-24 h after instillation of naked pDNA, then decreased to a level similar to 3 h at 48 h.


CONCLUSIONS
Gastric serosal surface in stillation of naked pDNA can be a highly stomach-selective gene transfer method in rats.
Nishi
Junya
J
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Fumoto
Shintaro
S
Ishii
Hiroki
H
Kodama
Yukinobu
Y
Nakashima
Mikiro
M
Sasaki
Hitoshi
H
Nakamura
Junzo
J
Nishida
Koyo
K
D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D005753:Gastric Mucosa / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008297:Male; D010957:Plasmids / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012704:Serous Membrane / Q000378:metabolism; D013997:Time Factors
D004247:DNA; D049409:Luciferases, Firefly