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Generation of alpha1,3-galactosyltransferase and cytidine monophospho-N-acetylneuraminic acid hydroxylase gene double-knockout pigs

Research Project

Project/Area Number 26870630
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General surgery
Integrative animal science
Research InstitutionMeiji University

Principal Investigator

Matsunari Hitomi  明治大学, 研究・知財戦略機構, 特任講師 (70639517)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords異種移植 / ブタ / ゲノム編集 / 体細胞核移植 / 臓器移植 / 遺伝子ノックアウト / 移植・再生医療 / トランスレーショナルリサーチ
Outline of Final Research Achievements

Pig to human xenotransplantation is one of the current strategies for overcoming the worldwide shortage of organ transplants. However, discordant xenografts involve severe immune rejections strongly related to species-specific glycoantigens. The major xenoantigen is the α-Gal epitope. Another carbohydrate xenoantigen, N-glycolylneuraminic acid (Neu5Gc), which is a component of the H-D antigen, has also been identified. Neu5Gc is synthesized by cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). The aim of this study was to produce α1,3-galactosyltransferase (GalT)/CMAH-double KO pigs using genome editing and somatic cell nuclear transfer (SCNT) technology. The homozygous CMAH KO cells were established using ZFNs or TALENs. These cells were used for SCNT and produced GalT/CMAH-double KO cloned pigs. The absence of α-Gal and H-D antigens was confirmed in both the tissue and granulocyte samples of the cloned piglets.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (6 results)

All 2015 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Generation of α1,3-galactosyltransferase and cytidine monophospho-<i>N</i>-acetylneuraminic acid hydroxylase gene double-knockout pigs2015

    • Author(s)
      Miyagawa S, Matsunari H, Watanabe M, Nakano K, Umeyama K, Sakai R, Takayanagi S, Takeishi T, Fukuda T, Yashima S, Maeda A, Eguchi H, Okuyama H, Nagaya M, Nagashima H.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 61 Issue: 5 Pages: 449-457

    • DOI

      10.1262/jrd.2015-058

    • NAID

      130005104116

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Production of alpha 1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-knockout pigs by genome editing and somatic cell cloning2015

    • Author(s)
      Matsunari H, Watanabe M, Nakano K, Uchikura A, Asano Y, Hatae S, Takeishi T, Yashima S, Fukuda T, Sakai S, Umeyama K, Nagaya M, Maeda A, Eguchi H, Okuyama H, Miyagawa S, Nagashima H.
    • Organizer
      2015 IPITA・IXA・CTS JOINT CONGRESS
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] α-ガラクトシル抗原およびH-D抗原を発現しない遺伝子ノックアウトブタの作出2015

    • Author(s)
      松成ひとみ,渡邊將人,中野和明,内倉鮎子,浅野吉則,武石透輝,福田暢,八島紗耶香,梅山一大,高柳就子,坂井理恵子,前田晃,江口寛,奥山宏臣,宮川周士,長嶋比呂志
    • Organizer
      第17回日本異種移植研究会
    • Place of Presentation
      自治医科大学(栃木県・下野市)
    • Year and Date
      2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Production efficiency of gene knockout pigs using genome editing and somatic cell cloning2015

    • Author(s)
      Hitomi Matsunari, Masahito Watanabe, Kazuaki Nakano, Ayuko Uchikura, Yoshinori Asano, Shota Hatae, Toki Takeishi, Kazuhiro Umeyama, Masaki Nagaya, Shuji Miyagawa, Yutaka Hanazono, Hiromitsu Nakauchi, Hiroshi Nagashima
    • Organizer
      41st Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Versailles (France)
    • Year and Date
      2015-01-12
    • Related Report
      2014 Research-status Report
  • [Remarks] 明治大学バイオリソース研究国際インスティテュート

    • URL

      http://muiibr.com

    • Related Report
      2015 Annual Research Report
  • [Remarks] 明治大学バイオリソース研究国債インスティテュート(MUIIBR)

    • URL

      http://muiibr.com

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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