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Development of organoid gene analysis system elucidating individual differences in cancer.

Research Project

Project/Area Number 22K19575
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionNational Cancer Center Japan

Principal Investigator

SEKINE KEISUKE  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (00323569)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords癌オルガノイド / オルガノイド / 膵癌 / ゲノム編集
Outline of Research at the Start

膵癌はその進行が早いことから手術検体からがん細胞を樹立して抗癌剤アッセイや網羅的遺伝子発現解析等を実施して薬剤を選別するには時間的猶予が無いことなどが、研究を進める上でのジレンマとして存在していた。そこで、本研究では上記のジレンマを解消するブレイクスルーとして、VUS(Variants of Uncertain Significance)を含む真に重要な遺伝子変異とゲノム背景を明らかにするため、癌の個性に迫るための効率の良いオルガノイド遺伝子改変技術の開発をめざす。

Outline of Final Research Achievements

We constructed a model system by introducing a gene expressing the fluorescent protein BFP into primary cancer cells and performing a genetic modification where a single amino acid substitution in BFP converts its fluorescence to GFP. Using this model system, we conducted studies and achieved a few percent gene modification efficiency. Firstly, we considered gene introduction for recombination to be a hurdle. Therefore, we explored gene delivery methods such as electroporation, gene delivery reagents, and introduction using Adeno-Associated Virus (AAV) vectors, and compared gene modification efficiencies using PrimeEditor.

Academic Significance and Societal Importance of the Research Achievements

癌の個性は遺伝子変異に加え、ゲノム背景や癌細胞の細胞特性に起因すると考えられるため、患者由来のプライマリ癌細胞が利用されるようになってきている。次世代シークエンス解析の発展により、VUS(Variants of Uncertain Significance)と呼ばれる臨床的意義不明のバリアントが多く見つかっており、VUSの機能解析を実施する為にはin vitroで操作可能な癌オルガノイドを対象とした効率の良い遺伝子改変技術の開発が不可欠であり、本研究ではVUSの機能解析に向けたゲノム編集技術の効率化検討が実施され、将来的な癌治療に向けた基礎研究の基盤になると期待される。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (11 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Development of a novel co-culture system using human pancreatic cancer cells and human iPSC-derived stellate cells to mimic the characteristics of pancreatic ductal adenocarcinoma in?vitro2023

    • Author(s)
      Kometani Tatsuya、Kamo Koki、Kido Taketomo、Hiraoka Nobuyoshi、Chibazakura Taku、Unno Kenji、Sekine Keisuke
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 658 Pages: 1-9

    • DOI

      10.1016/j.bbrc.2023.03.061

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development2022

    • Author(s)
      Krumm J, Sekine K, Samaras P, Brazovskaja A, Breunig M, Yasui R, Kleger A, Taniguchi H, Wilhelm M, Treutlein B, Camp JG, Kuster B
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 13 Pages: 110604-110604

    • DOI

      10.1016/j.celrep.2022.110604

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly Sensitive Detection of Human Pluripotent Stem Cells by Loop-Mediated Isothermal Amplification2022

    • Author(s)
      Yasui Ryota、Matsui Atsuka、Sekine Keisuke、Okamoto Satoshi、Taniguchi Hideki
    • Journal Title

      Stem Cell Reviews and Reports

      Volume: 18 Issue: 8 Pages: 2995-3007

    • DOI

      10.1007/s12015-022-10402-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] がん三次元培養モデルを用いた膵癌組織細胞間相互作用の解明2024

    • Author(s)
      関根圭輔
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ⼈為的がんモデルを⽤いたがん細胞社会の解明2022

    • Author(s)
      関根圭輔
    • Organizer
      第8回細胞凝集研究会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 患者由来癌モデルを用いたがんエコシステム解明2022

    • Author(s)
      関根圭輔
    • Organizer
      日本患者由来がんモデル学会2022学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] がん三次元培養モデルを用いた膵癌組織細胞間相互作用の解明2022

    • Author(s)
      関根圭輔
    • Organizer
      第4回がん三次元培養研究会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] がん研究入門コース(新技術)「オルガノイドを用いたがん研究」2022

    • Author(s)
      関根圭輔
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Elucidation and Control of Cancer Ecosystem using Artificial Cancer Tissue2022

    • Author(s)
      Keisuke Sekine
    • Organizer
      The 7th JCA-AACR Special Joint Conference
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Recapitulating pancreatic cancer ecosystems by multicellular cancer organoid cultures.2022

    • Author(s)
      Keisuke Sekine
    • Organizer
      AACR2022 Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 「がんゲノムペディア -77のキーワードで理解するゲノム医療とゲノム研究-」2024

    • Author(s)
      関根圭輔(柴田龍弘/編)
    • Total Pages
      255
    • Publisher
      羊土社
    • ISBN
      9784758121309
    • Related Report
      2023 Annual Research Report

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Published: 2022-07-05   Modified: 2025-01-30  

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