The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effe
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1237-TT05-11
The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effective and Safe Gene Delivery A. Tsuchiya1, T. Mori1, 2, Y. Naritomi1, J. –H. Kang1, D. Asai3, T. Niidome1, 2, Y. Endo4, R. Suzuki5, Y. Negishi4, K. Maruyama5, Y. Katayama1, 2 1 Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan 2 Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan 3 Department of Microbiology, St Marianna University School of Medicine, 2-16-1-Sugao Miyamae-ku, Kawasaki, 216-8511, Japan 4 Department of Drug and Gene Delivery System, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan 5 Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, 10911 Suwarashi, Sagamiko, Sagamihara, Kanagawa, 229-0155, Japan
Abstract We have developed new gene expression-regulating polymer that can activate transgene expression in response to target intracellular signals. Here, we tried applying sonoporation system to this gene regulation system to enhance the gene expression efficacy. Sonoporation is the method for effective gene transfection in vitro and in vivo. Therefore, the method might enhance the transfection efficiency in our polymer and realize an efficient and safe gene delivery system. Results suggested that the combination of our polymer and sonoporation could improve the gene expression compared to the system using only our polymer that transfers genes into cells via endocytosis. It also kept the ability of the gene regulation responding to cellular signals. Introduction Gene therapy has been expected as an effective treatment for cancer therapies. In fact, application of gene therapy to cancer treatment has occupied the major field in the clinical trial of this methodology. To improve the efficacy of the therapy, gene carriers transferring genes to cancer tissues are needed and, therefore, many carriers have been developed1). Several viral and non-viral carriers for gene transfer have been used for in vivo applications2), 3). Among those carriers, non-viral methods are currently increasing due to their lower risk as pathogenesis. Another important point in safe gene delivery is its cell specificity. Although many trials have been reported mainly by using active targeting strategy, sufficient cell specificity has not been accomplished. In our recent research, we exhibited a new gene-expression-regulatingsystem that can activate the transgene expression responding to pathologically activated protein kinase in tumor cells as a new concept of tumor cell selective gene delivery4), 5). Living cells are always responding to extracellular information and are regulating or modulating their gene expression. In these transduction pathways, protein kinases play one of the most important roles in cellular differentiation, proliferation and cell death. Various reports suggested that abnormal and continuou
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