Stomach-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Gastric Serosal Surface in Mice

• Published in: Biological & Pharmaceutical Bulletin Vol. 29; no. 10; pp. 2082 - 2086
• Main Authors: Nakamura, Junzo, Fumoto, Shintaro, Shoji, Keiko, Kodama, Yukinobu, Nishi, Junya, Nakashima, Mikiro, Sasaki, Hitoshi, Nishida, Koyo
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.10.2006; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Animals; DNA - administration & dosage; Gastric Mucosa - metabolism; gene therapy; Genetic Therapy - methods; luciferase; Male; Mice; mouse; plasmid DNA; Plasmids; stomach; Stomach Diseases - therapy; transfection
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.29.2082

The purpose of the present study was to achieve a stomach-selective gene transfer following the administration of naked plasmid DNA (pDNA) onto the gastric serosal surface in mice. Gene expression in the stomach and other tissues was evaluated by firefly luciferase activity. Six hours after gastric serosal surface instillation of naked pDNA, high gene expression in the stomach was observed. On the contrary, intravenous and intraperitoneal injection of naked pDNA exhibited no detectable gene expression. Following instillation of naked pDNA onto the gastric serosal surface, gene expression in the stomach was significantly higher than in other tissues. Gene expression in the stomach was highest 12 h after the instillation and thereafter decreased gradually. Utilizing a glass-made diffusion cell that is able to limit the contact dimension between the gastric serosal surface and the naked pDNA solution administered, site-specific gene expression in the stomach was achieved. This novel gene transfer method is expected to be a safe and effective treatment against serious stomach diseases.