人工染色体で難治性疾患治療に挑む
ヒト人工染色体を利用した難病の遺伝子細胞治療の実現に向けて研究しています
難病に指定されている疾患の中には、遺伝子のサイズが大き過ぎて、遺伝子治療が難しい疾患があります。
我々が独自の染色体工学技術を活用して開発した人工染色体はメガベース(Mb)サイズの巨大な遺伝子を搭載することができます。その利点を活かして、デュシェンヌ型筋ジストロフィーDMD遺伝子(2.4Mb)や毛細血管拡張性運動失調症ATM遺伝子(150Kb)などの原因遺伝子が大きな疾患をターゲットとした遺伝子細胞治療について研究しています。
これまでに、ヒトジストロフィン遺伝子全長(2.4Mb)を搭載したヒト人工染色体 (DYS-HAC)をマウスES細胞へ導入し、全身にDYS-HACが導入されたマウスを作出することに成功しています。さらに、内在性のマウスdmd遺伝子が完全に欠損したモデルマウスとDYS-HACマウスを交配することで、このマウスが病態を回復させるかを検討した結果、DYS-HAC ベクターにより組織学的・機能的異常を改善しました。また、毛細血管拡張性運動失調症ATM遺伝子(150Kb)を搭載したヒト人工染色体(ATM-HAC)を毛細血管拡張性運動失調症患者さん由来のiPS細胞へ導入することにも成功しています。
このように、染色体工学技術を用いて、これまで不可能であった難病疾患遺伝子治療の実現に向けて、日々研究しています。
挑戦的な研究に挑むことで革新が生まれるという信念を持って、研究に取り組んでいます。
論文一覧
2025年
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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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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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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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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
2025-01
DOI:
10.1016/j.biopha.2024.117751
2024年
-
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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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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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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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
-
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
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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
2022年
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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
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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
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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 51(2)
2022-11-15
DOI:
10.1124/dmd.122.001087
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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
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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
