Correction model of hemophilia A mice with multicopy of reprogramming factors and factor VIII gene using AC

• Project/Area Number: 26860733
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tottori University
• Principal Investigator: Kurosaki Hajime 鳥取大学, 医学(系)研究科(研究院), 助教 (70464295)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 血友病 / 幹細胞 / 再生医療 / 人工染色体ベクター / iPS細胞 / 細胞補充

Outline of Final Research Achievements

Artificial chromosome (AC) vectors have some unique characteristics as compared with conventional vectors, carrying large transgenes without size limitation, showing persistent expression of transgenes, and existing independently from host genome in cells. Hemophilia A (HA) is X chromosome-linked hemorrhagic disorder caused by defects in the coagulation factor VIII (FVIII) gene. Induced pluripotent stem (iPS) cells, which can be generated from an individual’s own tissues and contribute to any tissues, have a great potential for gene therapy. Induced-PS cells were generated from HA mouse embryonic fibroblasts by introducing AC vector with four reprogramming factors. The iPS cells were corrected by transferring AC vector with FVIII gene. The AC vector system, which contains the combination of reprogramming factors for making iPS cells and complement genes, may be a promising tool for safer gene- and cell-therapy of HA.

Research Products

• [Journal Article] Retargeting of microcell fusion towards recipient cell-oriented transfer of human artificial chromosome. (2015)
  • Author(s): Hiratsuka M, Ueda K, Uno N, Uno K, Fukuhara S, Kurosaki H, Takehara S, Osaki M, Kazuki Y, Kurosawa Y, Nakamura T, Katoh M, Oshimura M
  • Journal Title: BMC Biotechnol Volume: 15 Pages: 58-58
  • DOI: 10.1186/s12896-015-0142-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Upregulated lncRNA-UCA1 enhances therapeutic effect of oncolytic vaccinia virus in paclitaxel resistant ovarian cancer (2016)
  • Author(s): Kosuke Horita, Hajime Kurosaki, Motomu Nakatake, Nozomi kuwano, Kenta Ishii, Miyuki Nomura, Hiroaki Itamochi, Tetsuro Oishi, Tasuku Harada and Takafumi Nakamura
  • Organizer: The 22st Annual Meeting of Japan Society of Gene Therapy, Tokyo, 2016
  • Place of Presentation: Toranomon Hills forum, Tokyo, Japan
  • Year and Date: 2016-07-29
• [Presentation] Enhancing tumor specificity and therapeutic index of oncolytic vaccinia virus through deletions of both VGF and O1 protein genes (2015)
  • Author(s): Nakatake M, Yamane M, Parada R, Horita K, Okazaki M, Hasegawa K, Miyara A, Fujiwara K, Kurosaki H, Nakamura T
  • Organizer: The 21st Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Osaka International Convention Center, Nakanoshima, Kita-ku, Osaka, Japan
  • Year and Date: 2015-07-25
• [Presentation] Identification of host factors required for enhancing replication and spread of oncolytic vaccinia virus (2015)
  • Author(s): Horita K., Nakatake M., Goto I., Yamane M., Okazaki M., Rarada R., Kurosaki H., Nakamura T.
  • Organizer: The 21st Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Osaka International Convention Center, Nakanoshima, Kita-ku, Osaka, Japan
  • Year and Date: 2015-07-25
• [Presentation] Engineered integration-free iPS cells using artifidcial chromosome vectors for hemophilia A therapy (2015)
  • Author(s): Kurosaki H, Yakura Y, Hiratsuka M, Takehara S, Yoshino T, Kazuki Y, Nakamura T, Oshimura M
  • Organizer: The 21st Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Osaka International Convention Center, Nakanoshima, Kita-ku, Osaka, Japan
  • Year and Date: 2015-07-24
• [Presentation] ENGINEERED INTEGRATION-FREE iPS CELLS USING ARTIFICIAL CHROMOSOME VECTORS FOR HEMOPHILIA A THERAPY (2014)
  • Author(s): Hajime Kurosaki, Kana Ueda, Teruhiko Suzuki, Yuwna Yakura, Sayaka Fukuhara, Masaharu Hiratsuka, Shoko Takehara, Toko Yoshino, Yasuhiro Kazuki, Takafumi Nakamura and Mitsuo Oshimura
  • Organizer: 20th Annual Meeting of JSGT 2014
  • Place of Presentation: Jikei University School of Medicine (Daigaku Ichigou-kan), 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] DELETIONS OF BOTH VACCINIA GROWTH FACTOR AND O1 PROTEIN GENES ENHANCE THERAPEUTIC INDEX OF ONCOLYTIC VACCINIA VIRUS (2014)
  • Author(s): Naoyoshi Nitta, Ikumi Goto, Motomu Nakatake, Masato Yamane, Kosuke Horita, Hajime Kurosaki and Takafumi Nakamura
  • Organizer: 20th Annual Meeting of JSGT 2014
  • Place of Presentation: Jikei University School of Medicine (Daigaku Ichigou-kan), 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
  • Year and Date: 2014-08-06 – 2014-08-08
• [Remarks] 生体高次機能学部門
  • URL: http://www.med.tottori-u.ac.jp/integbio/5985.html