Eriko Kai1, Takahiro Ochiya. 1. Final Study Report Group, CDM Department, CMIC Co., Ltd., Shinagawa-ku, Tokyo 141-0022, Japan. eriko.kai@promega.com
Abstract
PURPOSE: The gastrointestinal tract poses a variety of morphological and physiological barriers to the expression of a target gene. In this work, N-acetylated chitosan is used as a gene delivery carrier for solving this problem. METHODS: Plasmid DNAs carrying the lacZ gene and interluekin-10 (IL-10) gene were mixed with N-acetylated chitosan. The N-acetylated chitosan/plasmid DNA complex was mixed into a food paste to feed mice. The transport and distribution characteristics of the plasmid along the intestinal mucosa were identified by beta-galactosidase assay. In addition, the stomach and intestines were subjected to analysis for the production of IL-10. RESULTS: The efficiency of N-acetylated chitosan-mediated gene delivery to the intestines was observed to be higher than that of chitosan alone. In particular, this result was most significant in the case of the duodenum, where the LacZ gene was expressed most effectively through the use of N-acetylated chitosan. It was also demonstrated that the IL-10 gene was successfully transferred to intestines through this method. CONCLUSIONS: A plasmid DNA was able to be orally delivered to the intestines using N-acetylated chitosan as a carrier. Thus, we have developed a dietary dose system for delivering a DNA vaccine for treating gastrointestinal diseases.
PURPOSE: The gastrointestinal tract poses a variety of morphological and physiological barriers to the expression of a target gene. In this work, N-acetylated chitosan is used as a gene delivery carrier for solving this problem. METHODS: Plasmid DNAs carrying the lacZ gene and interluekin-10 (IL-10) gene were mixed with N-acetylated chitosan. The N-acetylated chitosan/plasmid DNA complex was mixed into a food paste to feed mice. The transport and distribution characteristics of the plasmid along the intestinal mucosa were identified by beta-galactosidase assay. In addition, the stomach and intestines were subjected to analysis for the production of IL-10. RESULTS: The efficiency of N-acetylated chitosan-mediated gene delivery to the intestines was observed to be higher than that of chitosan alone. In particular, this result was most significant in the case of the duodenum, where the LacZ gene was expressed most effectively through the use of N-acetylated chitosan. It was also demonstrated that the IL-10 gene was successfully transferred to intestines through this method. CONCLUSIONS: A plasmid DNA was able to be orally delivered to the intestines using N-acetylated chitosan as a carrier. Thus, we have developed a dietary dose system for delivering a DNA vaccine for treating gastrointestinal diseases.
Authors: Michael D Buschmann; Abderrazzak Merzouki; Marc Lavertu; Marc Thibault; Myriam Jean; Vincent Darras Journal: Adv Drug Deliv Rev Date: 2013-07-18 Impact factor: 15.470