Development of novel gene delivery systems based on the function of biological molecules

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In this research project, we investigate the essential function of biological systems, such as viruses and chromosomes, which will be useful for developing novel non-viral devices for gene transfer and expression. The results we have obtained during the term of this project are summarized as below.1. We analyzed the mechanism of membrane fusion that will mediated efficient DNA delivery, and found that the membrane fusion requires essential non-receptor molecules which may be interacted with HN protein of Sendai virus.2. We establish the system to display various biological peptides on the surface of lambda phage particles, and propose to use this system to analyze the function of these peptides as components of non-viral gene delivery vehicles. Using this system, we showed that Tat peptide could enhance the delivery of lambda phage DNA into the cells and that NLS signal peptide of SV40 T antigen could target the lambda phage particles into the nucleus through the nuclear pore complex.3. We analyze the mechanism by which human chromosomes are stabilized in the nucleus, and found that the interaction between TRF1 and telomere repeat was involved in this process.4. We succeeded to cure mice with the disseminated cancer by treating them with the fusogenic liposomes encapsulating cancer-specific suicide gene.