About Tottori Bio Frontier

What can we do with human/mouse

What are Human/Mouse Artificial Chromosome Vectors?(*1 *2)

We utilized chromosome engineering technology developed at Tottori University to create a Human Artificial Chromosome (HAC) from human chromosome 21 and Mouse Artificial Chromosome (MAC) from a mouse chromosome.
These HAC and MAC vectors have special characteristics that are not found in conventional gene transfer vectors.

*1 Kazuki Y, Oshimura M. Mori Ther. 2011 *2 Takiguchi M. et al., ACS Synth Biol. 2012

We have received numerous awards in recognition of our chromosome engineering technology

  • Nikkei BP Medical and Biotechnology Prize (1998)
  • Japan Society of Human Genetics Academic Award (2002)
  • 10th Congress of the Japanese Society for Regenerative Medicine Young Investigator’s Award (2011)
  • 39th Annual Meeting of the Japanese Society of Toxicology Investigators’ Award (2012)
  • 117th OMICS Group Conference. International Conference on Genetic Engineering & Genetically Modified Organisms. Genetic Engineering-2013 OMICS Group Best Poster Award (2013)
  • 28th Japanese Society for the Study of Xenobiotics Award for Young Scientists (2013)

World-leading chromosome engineering technology is the key to an industrial innovation!

Drug Discovery Support Tools

Animal/cell models for human drug metabolism

Species differences exist in drug metabolism and dynamics between humans and experimental animals, and the results obtained from experimental animals do not always apply to humans. We therefore inserted genes involved in human drug metabolism into artificial chromosome vectors and created mice and rats containing these vectors. Those animals have been shown to reproduce drug metabolism in humans, and they may potentially reduce drug discovery costs.

Animal/cell models for human diseases

We use technology that we have developed to transfer chromosomes between cells to create model animals and cells that can reproduce diseases caused by chromosome abnormalities. We are currently pursuing research to reproduce Down Syndrome (trisomy of human chromosome 21) and explain its mechanisms. In the future, we hope to collaborate with drug manufacturers to develop therapeutic agents using these model animals and cells.

Source: FY 2013 Grant-in-Aid for Scientific Research (S) (FY 2013 - 2017)

Safety and Toxicity Assessment System

Animals/cells with reporter genes

The benefits of resistance to silencing of target gene expression and stable retention of genes for a given copy number as well as the ability to insert multiple reporter genes at once can be used to achieve simultaneous assessment and analysis of safety and toxicity in pharmaceuticals and food products.

Source: Development of globally pioneering toxicity test method required for new chemical regulations for petroleum refinery substances and other substances (Development of techniques for testing hepatotoxicity, nephrotoxicity, and neurotoxicity in vitro) for the Ministry of Economy, Trade and Industry (FY 2011-2015)

Gene Therapy and Regenerative Medicine

Vector to treat Duchenne muscular dystrophy

Utilizing the benefit that there is no limit to the size of genes that can be inserted, we are attempting to develop a treatment method in which we insert the entire 2.4 Mb of the human dystrophin gene into an artificial chromosome vector and transplant pluripotent cell bearing that chromosome into patients after differentiation into the appropriate cells.

Vector to treat hemophilia

We found that inserting multiple copies of target genes into artificial chromosome vectors results in copy number-dependent gene expression. This method may help augment the therapeutic effects of treatment for hemophilia and other diseases.
See the leaflet insert for details.

Bio-pharmaceutical Development

Complete human antibody-producing rats

We are creating rats that contain MAC vectors with entire human antibody genes in order to efficiently create effective bio-pharmaceuticals.

Source: Basic Science and Platform Technology Program for Innovative Biological Medicine, Ministry of Education, Culture, Sports, Science and Technology (FY 2014 - 2018)

High-yield antibody- or protein-producing cells

Artificial chromosome vectors can be used to greatly boost the long-term, stable expression of target genes in cells that are resistant to silencing. These cells offer a much higher yield of proteins with less variable quality between clones obtained than in the past.