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Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice


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Title: Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice
Authors: Nishi, Junya / Fumoto, Shintaro / Ishii, Hiroki / Kodama, Yukinobu / Nakashima, Mikiro / Sasaki, Hitoshi / Nakamura, Junzo / Nishida, Koyo
Issue Date: Jun-2008
Publisher: Elsevier
Citation: European Journal of Pharmaceutics and Biopharmaceutics, 69(2), pp.633-639; 2008
Abstract: Stomach-selective gene transfer is a promising approach as a therapeutic strategy for refractory gastric diseases. In this study, we improved the stomach selectivity of gene expression following microinstillation of naked plasmid DNA (pDNA) onto the gastric serosal surface in mice. pDNA encoding firefly luciferase was used as a reporter gene. It was confirmed that the gene expression level in the stomach 6 h after gastric serosal surface microinstillation of pDNA was significantly higher than after intragastric, intraperitoneal and intravenous administration. Regarding selectivity of gene expression, the gene expression level in the stomach after gastric serosal surface microinstillation of 1 μg/1 μL (dose/volume) pDNA was 5.7 times higher than that in the spleen. In our previous study (30 μg/30 μL), the expression level in the stomach was 2.7 times higher than that in the spleen; therefore, the selectivity was 2.1 times higher in this study. When we investigated gene expression at various pDNA solution concentrations, the ratio of the gene expression level in the stomach to that in the spleen was the highest as 1 μg/1 μL of pDNA, which was considered the optimal concentration. Information in this study is useful for further development of target organ-selective gene delivery systems.
Keywords: Gene delivery / Targeting / Stomach / Gene therapy / Plasmid DNA / Mouse / Luciferase
URI: http://hdl.handle.net/10069/16918
ISSN: 09396411
DOI: 10.1016/j.ejpb.2007.12.018
Rights: Copyright © 2007 Elsevier B.V. All rights reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/16918

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