Future Medicine Education and Research Organization at Chiba University

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  • DNA vaccine technology based on nanoparticle encapsulating DNA (and having adjuvant effect on dendritic cell activity) More details

    Summary

    ・Delivery of antigen protein-encoding DNA into the nuclear of target immune cells, in particular, of antigen-presenting dendritic cells for the antigen-specific T-cell activation. To accomplish this, we developed a DNA-encapsulating lipid nanoparticle in those lipid derivative of α-helical peptide was modified. Along with a gene transfection, the transfection of this particle then resulted in an immune-stimulation (i.e. cytokine production of type-I interferon). This is to the technology for the antigen presentation of cancer cell-specific polypeptides on the surface of dendritic cells that will be helpful to realize the immune-therapy for the cure of malignant tumor.
    ・Conventional methods do not, however, conferred an efficient nuclear uptake of DNA in dendritic cell.
    ・Thus, the purpose of this research is to achieve efficient control of the intracellular trafficking of DNA for the nuclear delivery of dendritic cells.

    Inventors

    Hidetaka Akita

  • Selective inhibition of DNA methylation based on molecules that bind to DNAMore details

    Summary

    ・Aberrant and hyper DNA methylation of gene promoter regions that regulate the expression of genes affect transcription of genes. Thus, aberrant and hyper DNA methylation of gene promoter regions relative to tumor suppressor genes constitutes significant cause of tumor genesis in colorectal cancer and in many other cancers.
    ・From the perspective of cancer therapy, there is need of exploration of means that selectively target the methylated promoter regions with a view of raising the expression of tumor suppressor genes.
    ・Researchers developed a method for selective inhibition of DNA methylation based on molecules that bind to DNA.

    Inventors

    Atsushi Kaneda

  • Therapeutic agent for fibrosis and inhibitor of nuclear accumulation of phosphorylated Smad More details

    Summary

    ・Available data are said to suggest that the prevalence rate of Idiopathic pulmonary fibrosis (IPF) would be such that ten to twenty people of ten thousand people are affected, but the number of potential patients is assumed to be more than tenfold. Because the cause of the disease is unknown, and there is no established medical treatment, IPF is designated as an intractable disease in Japan.
    ・Pirfenidone and Nintedanib are the two therapeutic agents that are approved in Japan. Whilst these conventional therapeutic agents help managing the forced vital capacity, they are not capable of extending survival in patients. As such, there is need for a therapeutic agent based on novel approaches.
    ・The inventor revealed that glucosylceramide (GlcCer) synthase inhibitor or lactosylceramide (LacCer) synthase inhibitor inhibits nuclear accumulation of phosphorylated Smad, thereby suppresses expression of collagen and α-SMA, which cause fibrosis. A new mechanism of action was found in the field of therapy and prevention of fibrosis.

    Inventors

    Hiroyuki Nakamura, Toshihiko Murayama

  • Therapeutic agent for Niemann-Pick disease type C More details

    Summary

    ・Niemann-Pick disease type C (NPC) is characterized by accumulation of cholesterol in cells caused by cholesterol transport disorder in cells. Conventional therapies cannot improve a cholesterol transport disorder.
    ・Researchers demonstrated the effect of ceramide 1-phosphate (C1P) inhibitor on the accumulation of cholesterol in NPC disease cellular model. Based on that, researchers strive to develop a novel therapeutic agent for NPC, the action mechanism of which consists of remedy of cholesterol transport disorder by suppression of ceramide kinase.

    Inventors

    Hiroyuki Nakamura, Toshihiko Murayama

  • Nanoparticle formulation of drug crystals More details

    Summary

    ・Nanonization of drugs is one of the methods of improving poorly water-soluble drugs’ solubility as well as bioavailability which represents the rate of drug absorption into human body.
    ・Current methods of nanonization of drugs include dry milling, coprecipitation, and the like. However, each of these current methods has its shortcomings.
    ・Inventors achieved nanoparticle formulation of drug crystals through hot melt extruder. Proper setting of composition ratio of the mixture (water-soluble polymers, surfactants, and the like) and the heating temperature obtains pellets with dispersed nanocrystal drugs. It is superior to conventional drug nanocrystals preparation methods in that organic solvent is unnecessary and volume production in simplified processes and in continuous processes is achievable, both of which are not existent in current formulation of nanocrystals.

    Inventors

    Kenjiro Higashi, Kunikazu Moribe

  • Suppression of tumoral metastasis and invasiveness via the control of cell-to-cell adhesion networks More details

    Summary

    ・It was clear that when an excessive expression of Lin7C was introduced, the Lin7C-Cask-βcatenin network was activated and metastasisation was suppressed.
    ・we have identified Mirtazapine as the most effective pharmaceutical reagent out of six reagents characterized as ligands for, thus agonists to, the gene HTR2C that is an upstream molecule of the Lin7C-Cask-βcatenin network, and through the use of the reagent we have made possible the suppression of invasiveness and migration.

    Inventors

    Hideki Tanzawa