デザイナー細胞・動物の創成と応用
染色体工学技術を用いたデザイナー細胞・動物による基礎研究と
創薬研究に取り組んでいます
我々は独自の染色体工学技術を活用し、ヒト21番染色体をベースにヒト人工染色体（HAC）を構築してきました。
この染色体は遺伝子領域を極限まで削り、主にセントロメア、複製起点、テロメアからなります。
HACをベクターとして活用する際の最大の特徴は、数メガベースに及ぶ染色体レベルの遺伝子導入が可能なことです。
一方、ヒト由来セントロメア配列を持つHACベクターのマウスでの安定性は完全とは言えず、課題として残っていました。
この問題を解決すべく、私たちはマウスの染色体をベースに新たにマウス人工染色体（MAC）を構築しました。
これまでにHAC/MAC技術を活用し、Mb単位の巨大なヒト遺伝子クラスターのマウス・ラットへの導入、
すなわちトランスクロモソミック(Trans-chromosomic: TC)マウス・ラットの作製に世界で初めて成功しました。
これまでにヒト薬物代謝酵素遺伝子クラスター(1.5Mb) 、ヒト抗体遺伝子群（3.5Mb）等を上記HAC/MACベクターに搭載することに成功しています。
さらに、HAC/MACへ巨大遺伝子を搭載した、いわば「Designed Chromosome」をマウスやラットに導入することで「Designed Animal」を作製し、
疾患モデルマウスの発症メカニズムの解明と治療研究、完全ヒト抗体産生動物による抗体医薬品シーズの作製、
薬物動態モデル動物による安全性評価、患者由来iPS細胞による遺伝子細胞治療研究等、に取り組んできました。
さらに、「Designed Chromosome」を用いた「Designed Cell」による基礎研究から創薬研究にも取り組んでいます。
論文一覧
2026年
-
Rapid immunization and antibody redesign platform discovers broadly neutralizing antibodies against non-immunized SARS-CoV-2 variant.
Shusei Hamamichi, Narumi Uno, Kazuto Shimoya, Takato Fukushima, Marina Abe, Arata Watanabe, Mizuho Ito, Yuko Wakasa, Yuko Yajima, Rio Suzuki, Natsumi Miyazaki, Akifumi Kamiyama, Kana Uno, Masaharu Hiratsuka, Takashi Moriwaki, Tomokazu Tamura, Kyosuke Kanai, Satoshi Abe, Takasuke Fukuhara, Seiji Kageyama, Masayuki Su'etsugu, Yasuhiro Kazuki, Kazuma Tomizuka
Molecular therapy : the journal of the American Society of Gene Therapy 34(1)
2026-01-07
DOI:
10.1016/j.ymthe.2025.10.020
2025年
-
Establishment of immortalized ovarian stromal cell lines using Sendai virus vectors: a platform for studying tumor-stroma interactions and carcinogenesis.
Masayo Okawa, Hiroaki Komatsu, Yasuhiro Kazuki, Kanako Kazuki, Genki Hichiwa, Kohei Hikino, Yuki Iida, Mayumi Sawada, Hiroyuki Kugoh, Shinya Sato, Mitsuo Oshimura, Tasuku Harada, Fuminori Taniguchi
Human cell 39(1)
2025-11-26
DOI:
10.1007/s13577-025-01324-6
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Matrix Metalloproteinase-1 as an Independent Prognostic Biomarker in Epithelial Ovarian Carcinoma.
Kohei Hikino, Hiroaki Komatsu, Yasuhiro Kazuki, Kanako Kazuki, Koji Yamamoto, Masayo Okawa, Yuki Iida, Mayumi Sawada, Genki Hichiwa, Shinya Sato, Hiroyuki Kugoh, Mitsuo Oshimura, Tasuku Harada, Fuminori Taniguchi
Anticancer research 45(10)
2025-10
DOI:
10.21873/anticanres.17795
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CXCL14 is an essential modulator of TLR9 agonist-induced antitumor immune responses.
Kosuke Tanegashima, Eiji Esashi, Koji Ishida, Ayumi Kotaki, Rina Iwase, Manaka Hasebe, Rena Takahashi, Risa Saito, Yasuhiro Kazuki, Teruhiko Suzuki, Takahiko Hara
Journal of immunology (Baltimore, Md. : 1950) 214(8)
2025-08-01
DOI:
10.1093/jimmun/vkaf080
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Targeting of bowel tissue by fully human antibodies cross-reactive with human and mouse GPA33 antigen.
Genki Hichiwa, Abdur Rafique, Asaki Nagashima, Yayan Wang, Kanako Kazuki, Ryohei Ogihara, Muhammad Feisal Jatnika, Ryosuke Shimamoto, Yumi Iwai, Narumi Uno, Hiroyuki Satofuka, Kazuma Tomizuka, Yuji Ito, Yasuhiro Kazuki
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 189
2025-08
DOI:
10.1016/j.biopha.2025.118336
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Generation of transchromosomic mice harboring HLA-A/B/C and human B2M via mouse artificial chromosome and triple BAC integration.
Nanami Kishima, Takashi Moriwaki, Narumi Uno, Teruhiko Suzuki, Satoshi Abe, Masaki Sugawara, Yuichi Nagashima, Kanako Kazuki, Takeshi Endo, Kyotaro Yamazaki, Wakana Nakagawa, Reika Yuno, Yui Moriguchi, Satoko Matsukura, Kazuma Tomizuka, Yasuhiro Kazuki
Scientific reports 15(1)
2025-07-30
DOI:
10.1038/s41598-025-13138-5
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Double-humanized Rats for CYP3A and PXR as an Improved Model for Analyzing Drug-drug Interactions Mediated by CYP3A4.
Kaoru Kobayashi, Genki Minegishi, Kanako Kazuki, Satoshi Abe, Miyuki Sato, Atsushi Miyajima, Masumi Hirabayashi, Tetsushi Sakuma, Takashi Yamamoto, Yasuhiro Kazuki
The AAPS journal 27(5)
2025-07-28
DOI:
10.1208/s12248-025-01111-z
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Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants.
Yuki Anraku, Shunsuke Kita, Taishi Onodera, Akihiko Sato, Takashi Tadokoro, Shiori Ito, Yu Adachi, Ryutaro Kotaki, Tateki Suzuki, Jiei Sasaki, Nozomi Shiwa-Sudo, Naoko Iwata-Yoshikawa, Noriyo Nagata, Souta Kobayashi, Yasuhiro Kazuki, Mitsuo Oshimura, Takao Nomura, Michihito Sasaki, Yasuko Orba, Tadaki Suzuki, Hirofumi Sawa, Takao Hashiguchi, Hideo Fukuhara, Yoshimasa Takahashi, Katsumi Maenaka
Communications biology 8(1)
2025-03-22
DOI:
10.1038/s42003-025-07827-0
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Development of an OATP1-humanized transchromosomic mouse model for prediction of hepatic drug uptake in humans.
Tomoki Koishikawa, Kanako Kazuki, Rina Ohnishi, Koki Okita, Tadahaya Mizuno, Satoshi Abe, Isamu Nanchi, Yusaku Masago, Kyotaro Yamazaki, Jun-Ichiro Ohzeki, Hiroyuki Kusuhara, Yasuhiro Kazuki
Drug metabolism and disposition: the biological fate of chemicals 53(2)
2025-02
DOI:
10.1016/j.dmd.2024.100028
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Titin fragment is a sensitive biomarker in Duchenne muscular dystrophy model mice carrying full-length human dystrophin gene on human artificial chromosome.
Yosuke Hiramuki, Miwa Hosokawa, Kayo Osawa, Taku Shirakawa, Yasuhiro Watanabe, Ritsuko Hanajima, Hiroyuki Kugoh, Hiroyuki Awano, Masafumi Matsuo, Yasuhiro Kazuki
Scientific reports 15(1)
2025-01-13
DOI:
10.1038/s41598-025-85369-5
2024年
-
Human artificial chromosome carrying R-spondin1 and IL-22 expression cassettes in rejuvenated MSCs enhances therapeutic efficacy in ulcerative colitis model mice.
Yayan Wang, Kanako Kazuki, Genki Hichiwa, Masaharu Hiratsuka, Ryohei Ogihara, Satoshi Abe, Haochen Tu, Yanze Li, Xu Gao, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 182
2024-12-17
DOI:
10.1016/j.biopha.2024.117751
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Microcell-mediated chromosome transfer between non-identical human iPSCs
Narumi Uno, Hitomaru Miyamoto, Kyotaro Yamazaki, Masaya Egawa, Hiroaki Kobayashi, Kanako Kazuki, Mitsuhiko Osaki, Teruhiko Suzuki, Shusei Hamamichi, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Molecular Therapy - Nucleic Acids 35(4)
2024-12
DOI:
10.1016/j.omtn.2024.102382
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Mice carrying the full-length human immunoglobulin loci produce antigen-specific human antibodies with the lambda light chain
Kazuto Shimoya, Takashi Moriwaki, Kanako Kazuki, Akane Okada, Shigenori Baba, Yuana Masuda, Satoshi Abe, Yasuhiro Kazuki
iScience 27(12)
2024-12
DOI:
10.1016/j.isci.2024.111258
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Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9‐Mediated Interstitial Megabase Deletion
Masaya Egawa, Narumi Uno, Rina Komazaki, Yusuke Ohkame, Kyotaro Yamazaki, Chihiro Yoshimatsu, Yuki Ishizu, Yusaku Okano, Hitomaru Miyamoto, Mitsuhiko Osaki, Teruhiko Suzuki, Kazuyoshi Hosomichi, Yasunori Aizawa, Yasuhiro Kazuki, Kazuma Tomizuka
Genes to Cells 30(1)
2024-11-24
DOI:
10.1111/gtc.13184
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Rejuvenation of human mesenchymal stem cells using a nonintegrative and conditionally removable Sendai virus vector.
Mitsuo Oshimura, Toshiaki Tabata, Narumi Uno, Shuta Takata, Genki Hichiwa, Iori Kanazawa, Takeshi Endo, Kazuhisa Honma, Yayan Wang, Kanako Kazuki, Haochen Tu, Yuichi Iida, Satoshi Abe, Yasuhiro Kazuki
Scientific reports 14(1)
2024-10-09
DOI:
10.1038/s41598-024-74757-y
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Developing a workflow for the isolation of hybridoma cells producing fully human antigen-specific antibodies using a surface IgG detection method.
Hiroyuki Satofuka, Yayan Wang, Hiroshi Tanaka, Kei Hiramatsu, Kayoko Morimoto, Haruka Takayama, Haochen Tu, Yu Qiao, Satoru Ito, Xu Gao, Mitsuo Oshimura, Yasuhiro Kazuki
Scientific reports 14(1)
2024-10-04
DOI:
10.1038/s41598-024-73770-5
-
Characterization of immortalized ovarian epithelial cells with BRCA1/2 mutation.
Hiroaki Komatsu, Masayo Okawa, Yasuhiro Kazuki, Kanako Kazuki, Genki Hichiwa, Kazuto Shimoya, Shinya Sato, Fuminori Taniguchi, Mitsuo Oshimura, Tasuku Harada
Human cell 37(4)
2024-07
DOI:
10.1007/s13577-024-01064-z
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Induction of hepatic CYP3A4 expression by cholesterol and cholic acid: Alterations of gene expression, microsomal activity, and pharmacokinetics.
Genki Minegishi, Yuka Kobayashi, Mayu Fujikura, Ayane Sano, Yasuhiro Kazuki, Kaoru Kobayashi
Pharmacology research & perspectives 12(3)
2024-06
DOI:
10.1002/prp2.1197
-
医学用語解説 完全ヒト抗体産生動物を用いたヒト抗体作製
濱道 修生, 森脇 崇史, 香月 康宏
炎症と免疫 32(3)
2024-04
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Vincristine Disposition and Neurotoxicity Are Unchanged in Humanized CYP3A5 Mice.
Yang Li, Yasuhiro Kazuki, Thomas Drabison, Kaoru Kobayashi, Ken-Ichi Fujita, Yue Xu, Yan Jin, Eman Ahmed, Junan Li, Eric D Eisenmann, Sharyn D Baker, Guido Cavaletti, Alex Sparreboom, Shuiying Hu
Drug metabolism and disposition: the biological fate of chemicals 52(2)
2024-01-09
DOI:
10.1124/dmd.123.001466
-
Rapid human genomic DNA cloning into mouse artificial chromosome via direct chromosome transfer from human iPSC and CRISPR/Cas9-mediated translocation.
Hitomaru Miyamoto, Hiroaki Kobayashi, Nanami Kishima, Kyotaro Yamazaki, Shusei Hamamichi, Narumi Uno, Satoshi Abe, Yosuke Hiramuki, Kanako Kazuki, Kazuma Tomizuka, Yasuhiro Kazuki
Nucleic acids research 52(3)
2024-01-05
DOI:
10.1093/nar/gkad1218
2023年
-
Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome
Nobuhiro Kurabayashi, Kazuki Fujii, Yuta Otobe, Shingo Hiroki, Masaharu Hiratsuka, Hikari Yoshitane, Yasuhiro Kazuki, Keizo Takao
iScience 26(12)
2023-11
DOI:
10.1016/j.isci.2023.108379
-
【ヒト化動物の最新研究】ヒト化動物を用いた薬物代謝・動態研究への応用
小林 カオル, 香月 康宏
実験動物ニュース 72(4)
2023-10
-
Phenotypic features of dystrophin gene knockout pigs harboring a human artificial chromosome containing the entire dystrophin gene.
Masahito Watanabe, Hitomaru Miyamoto, Kazutoshi Okamoto, Kazuaki Nakano, Hitomi Matsunari, Kanako Kazuki, Koki Hasegawa, Ayuko Uchikura, Shuko Takayanagi, Kazuhiro Umeyama, Yosuke Hiramuki, Elisabeth Kemter, Nikolai Klymuik, Mayuko Kurome, Barbara Kessler, Eckhard Wolf, Yasuhiro Kazuki, Hiroshi Nagashima
Molecular therapy. Nucleic acids 33
2023-09-12
DOI:
10.1016/j.omtn.2023.07.021
-
ncBAF enhances PXR-mediated transcriptional activation in the human and mouse liver.
Kiamu Kurosawa, Masataka Nakano, Itsuki Yokoseki, Mai Nagaoka, Seiya Takemoto, Yoshiyuki Sakai, Kaoru Kobayashi, Yasuhiro Kazuki, Tatsuki Fukami, Miki Nakajima
Biochemical pharmacology
2023-08-03
DOI:
10.1016/j.bcp.2023.115733
-
Co-treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency
Narumi Uno, Hiroyuki Satofuka, Hitomaru Miyamoto, Kazuhisa Honma, Teruhiko Suzuki, Kyotaro Yamazaki, Ryota Ito, Takashi Moriwaki, Shusei Hamamichi, Kazuma Tomizuka, Mitsuo Oshimura, Yasuhiro Kazuki
Molecular Therapy - Nucleic Acids
2023-07
DOI:
10.1016/j.omtn.2023.07.002
-
Full-length human dystrophin on human artificial chromosome compensates for mouse dystrophin deficiency in a Duchenne muscular dystrophy mouse model
Yosuke Hiramuki, Satoshi Abe, Narumi Uno, Kanako Kazuki, Shuta Takata, Hitomaru Miyamoto, Haruka Takayama, Kayoko Morimoto, Shoko Takehara, Mitsuhiko Osaki, Jun Tanihata, Shin’ichi Takeda, Kazuma Tomizuka, Mitsuo Oshimura, Yasuhiro Kazuki
Scientific Reports 13(1)
2023-03-16
DOI:
10.1038/s41598-023-31481-3
-
Characterization of human anti-EpCAM antibodies for developing an antibody–drug conjugate
Hiroyuki Satofuka, Yayan Wang, Kyotaro Yamazaki, Shusei Hamamichi, Takeshi Fukuhara, Abdur Rafique, Nana Osako, Iori Kanazawa, Takeshi Endo, Naomi Miyake, Kazuhisa Honma, Yuichi Nagashima, Genki Hichiwa, Kazuto Shimoya, Satoshi Abe, Takashi Moriwaki, Yasufumi Murakami, Xu Gao, Hiroyuki Kugoh, Mitsuo Oshimura, Yuji Ito, Yasuhiro Kazuki
Scientific Reports 13(1)
2023-03-14
DOI:
10.1038/s41598-023-31263-x
-
Publisher Correction: Simultaneous loading of PCR-based multiple fragments on mouse artificial chromosome vectors in DT40 cell for gene delivery.
Kyotaro Yamazaki, Kyosuke Matsuo, Akane Okada, Narumi Uno, Teruhiko Suzuki, Satoshi Abe, Shusei Hamamichi, Nanami Kishima, Shota Togai, Kazuma Tomizuka, Yasuhiro Kazuki
Scientific reports 13(1)
2023-02-28
DOI:
10.1038/s41598-023-30359-8
-
Pathological Comparison of TDP-43 Between Motor Neurons and Interneurons Expressed by a Tetracycline Repressor System on the Mouse Artificial Chromosome.
Shota Togai, Shusei Hamamichi, Yasuhiro Kazuki, Masaharu Hiratsuka
Yonago acta medica 66(1)
2023-02
DOI:
10.33160/yam.2023.02.004
2022年
-
Simultaneous loading of PCR-based multiple fragments on mouse artificial chromosome vectors in DT40 cell for gene delivery.
Kyotaro Yamazaki, Kyosuke Matsuo, Akane Okada, Narumi Uno, Teruhiko Suzuki, Satoshi Abe, Shusei Hamamichi, Nanami Kishima, Shota Togai, Kazuma Tomizuka, Yasuhiro Kazuki
Scientific reports 12(1)
2022-12-16
DOI:
10.1038/s41598-022-25959-9
-
Analysis of in vitro and in vivo metabolism of zidovudine and gemfibrozil in trans-chromosomic mouse line expressing human UGT2 enzymes.
Kaoru Kobayashi, Tsuneo Deguchi, Satoshi Abe, Naoyo Kajitani, Kanako Kazuki, Shoko Takehara, Kazuomi Nakamura, Atsushi Kurihara, Mitsuo Oshimura, Yasuhiro Kazuki
Pharmacology research & perspectives 10(6)
2022-12
DOI:
10.1002/prp2.1030
-
Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci
Hiroyuki Satofuka, Satoshi Abe, Takashi Moriwaki, Akane Okada, Kanako Kazuki, Hiroshi Tanaka, Kyotaro Yamazaki, Genki Hichiwa, Kayoko Morimoto, Haruka Takayama, Yuji Nakayama, Shinya Hatano, Yutaro Yada, Yasufumi Murakami, Yoshihiro Baba, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Nature Communications 13(1)
2022-12
DOI:
10.1038/s41467-022-29421-2
-
Metabolic disposition of triazolam and clobazam in humanized CYP3A mice with a double knockout background of mouse Cyp2c and Cyp3a genes.
Kaoru Kobayashi, Genki Minegishi, Nina Kuriyama, Atsushi Miyajima, Satoshi Abe, Kanako Kazuki, Yasuhiro Kazuki
Drug metabolism and disposition: the biological fate of chemicals
2022-11-15
DOI:
10.1124/dmd.122.001087
-
マウス人工染色体ベクターを用いたHLA-A,B,C遺伝子領域保持マウスの作製と解析
岸間 菜々美, 森脇 崇史, 香月 加奈子, 中川 和奏, 宇野 愛海, 冨塚 一磨, 鈴木 輝彦, 香月 康宏
MHC: Major Histocompatibility Complex 29(2Suppl.)
2022-09
-
センダイウイルスを用いた正常卵巣およびBRCA-1/-2変異のある患者卵巣表層上皮不死化細胞株樹立と解析(Establishment of Sendai virus-mediated reversibly immortalized ovarian cell lines from normal and BRCA-1/2 mutation)
小松 宏彰, 香月 康宏, 香月 加奈子, 大川 雅世, 曳野 耕平, 飯田 祐基, 澤田 真由美, 細川 雅代, 工藤 明子, 千酌 潤, 佐藤 慎也, 谷口 文紀
日本癌学会総会記事 81回
2022-09
-
Humanized liver TK-NOG mice with functional deletion of hepatic murine cytochrome P450s as a model for studying human drug metabolism
Shotaro Uehara, Yuichi Iida, Miyuki Ida-Tanaka, Motohito Goto, Kenji Kawai, Masafumi Yamamoto, Yuichiro Higuchi, Satoshi Ito, Riichi Takahashi, Hidetaka Kamimura, Mamoru Ito, Hiroshi Yamazaki, Mitsuo Oshimura, Yasuhiro Kazuki, Hiroshi Suemizu
Scientific Reports 12(1)
2022-09-01
DOI:
10.1038/s41598-022-19242-0
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Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation.
Yuki Yamasaki, Takashi Moriwaki, Seiryo Ogata, Shingo Ito, Sumio Ohtsuki, Genki Minegishi, Satoshi Abe, Yumi Ohta, Kanako Kazuki, Kaoru Kobayashi, Yasuhiro Kazuki
Pharmacogenetics and genomics 32(8)
2022-08-22
DOI:
10.1097/FPC.0000000000000481
-
Panel of human cell lines with human/mouse artificial chromosomes.
Narumi Uno, Shuta Takata, Shinya Komoto, Hitomaru Miyamoto, Yuji Nakayama, Mitsuhiko Osaki, Ryota Mayuzumi, Natsumi Miyazaki, Chiaki Hando, Satoshi Abe, Tetsushi Sakuma, Takashi Yamamoto, Teruhiko Suzuki, Yoshihiro Nakajima, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Scientific reports 12(1)
2022-02-22
DOI:
10.1038/s41598-022-06814-3
-
A transchromosomic rat model with human chromosome 21 shows robust Down syndrome features.
Yasuhiro Kazuki, Feng J Gao, Miho Yamakawa, Masumi Hirabayashi, Kanako Kazuki, Naoyo Kajitani, Sachiko Miyagawa-Tomita, Satoshi Abe, Makoto Sanbo, Hiromasa Hara, Hiroshi Kuniishi, Satoshi Ichisaka, Yoshio Hata, Moeka Koshima, Haruka Takayama, Shoko Takehara, Yuji Nakayama, Masaharu Hiratsuka, Yuichi Iida, Satoko Matsukura, Naohiro Noda, Yicong Li, Anna J Moyer, Bei Cheng, Nandini Singh, Joan T Richtsmeier, Mitsuo Oshimura, Roger H Reeves
American journal of human genetics 109(2)
2022-02-03
DOI:
10.1016/j.ajhg.2021.12.015
-
An improved TK-NOG mouse as a novel platform for humanized liver that overcomes limitations in both male and female animals
Shotaro Uehara, Yuichiro Higuchi, Nao Yoneda, Kenji Kawai, Masafumi Yamamoto, Hidetaka Kamimura, Yuichi Iida, Mitsuo Oshimura, Yasuhiro Kazuki, Hiroshi Yamazaki, Hayato Hikita, Tetsuo Takehara, Hiroshi Suemizu
Drug Metabolism and Pharmacokinetics 42
2022-02
DOI:
10.1016/j.dmpk.2021.100410
