Annual Meeting of the Japanese Society of Toxicology
The 50th Annual Meeting of the Japanese Society of Toxicology
Session ID : SL4
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Special Lecture
Forefront of Toxicity Research by Chromosome Engineering Technology
*Yasuhiro KAZUKI
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CONFERENCE PROCEEDINGS FREE ACCESS

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Abstract

The development of vectors for expressing genes in mammalian cells and animals has not only been a tool for analyzing gene functions, but also has played an important role in industrial and medical applications. In the conventional transgenic technology, the DNA that can be introduced is usually limited to several hundred kb, and it has been impossible to introduce genes or gene clusters having a size exceeding 1 Mb. To solve these problems, we used chromosome engineering technology to develop human artificial chromosomes (HAC) and mouse artificial chromosomes (MAC) that can introduce large human genes, multiple human genes in a stable manner. We have succeeded in loading the human dystrophin gene (2.5Mb), the human drug-metabolizing enzyme gene cluster (1.5Mb), the human antibody genes (3.5Mb), etc. into the HAC/MAC vector. Furthermore, by introducing a "Designed Chromosome" into mice and rats, in which a large gene is loaded into HAC/MAC, "Designed Animals" were created. Using these animals, we have worked on drug metabolism and pharmacokinetic research, toxicity research, production of antibody drug candidates, etc. Furthermore, we are working on basic research and applied research by "Designed Cell" using "Designed Chromosome". In this presentation, I will introduce new drug discovery tools (fully human antibody-producing animal containing human Ig locus, mouse/rat (or human cell lines) expressing human drug metabolism, etc.) developed by HAC/MAC technology, and further introduce new combined technologies of DNA synthesis and HAC/MAC for biomedical research.

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