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ゲノム編集を駆使したシスエレメントの反復配列多型による遺伝子発現制御の理解

Research Project

Project/Area Number 23KF0041
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeMulti-year Fund
Section外国
Review Section Basic Section 43050:Genome biology-related
Research InstitutionKyoto University

Principal Investigator

ウォルツェン クヌート  京都大学, iPS細胞研究所, 准教授 (50589489)

Co-Investigator(Kenkyū-buntansha) MARTINEZ GALVEZ GABRIEL  京都大学, iPS細胞研究所, 外国人特別研究員
Project Period (FY) 2023-04-25 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2023: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsDNAリピート / ゲノム編集 / CRISPR-Cas9 / iPS細胞 / レポーターアッセイ
Outline of Research at the Start

Tandem repeat copy-number variations have been correlated with changes in gene expression and are probable causes of human disease. We are developing gene editing and computational biology methods to efficiently generate repeat-variant disease models in human induced pluripotent stem (iPS) cells. Moreover, we are developing technologies to produce intermediate copy-number variants. As proof-of-concept, we completed the generation of a repeat-copy variants in iPS cells at two loci with known clinically relevance, and aim to apply these methods genome-wide.

Outline of Annual Research Achievements

Variable Number Tandem Repeats (VNTRs) are repetitive DNA sequences that differ in number between individuals. VNTR copy number is shown to correlate with changes in gene expression, and are probable causes of human disease. To understand these relationships, we developed a new bioinformatic pipeline to identify, analyze, and design gene editing strategies for VNTRs, which has never been previously achieved. We characterized 5 VNTRs for copy-number polymorphisms across 22 human iPS cell lines. We designed CRISPR-Cas9 strategies that target and cut each repeats, triggering cellular DNA repair that reduces the repeat number to one. Moreover, we developed a novel gene editing strategy to control VNTR copy-number to generate iPS cells with VNTRs of various copy numbers for disease modeling.

Report

(1 results)
  • 2023 Annual Research Report
  • Research Products

    (9 results)

All 2024 2023

All Journal Article (1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] On the edge of deletion: Using natural and engineered microhomology to edit the human genome2024

    • Author(s)
      Martinez-Galvez Gabriel、Lee Suji、Niwa Ryo、Woltjen Knut
    • Journal Title

      Gene and Genome Editing

      Volume: 7 Pages: 100033-100033

    • DOI

      10.1016/j.ggedit.2024.100033

    • Related Report
      2023 Annual Research Report
  • [Presentation] Discovery and generation of polymorphic copy number variants in human induced Pluripotent Stem cells2024

    • Author(s)
      Xiaoyan Ren, Gabriel Felipe Martinez-Galvez, Knut Woltjen
    • Organizer
      CiRA Retreat 2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Genome Editing in Human iPS Cells for Modeling Infectious and Genetic Disease2024

    • Author(s)
      Knut Woltjen
    • Organizer
      ゲノム編集医療概論
    • Related Report
      2023 Annual Research Report
  • [Presentation] Discovery and generation of polymorphic copy number variants in human iPS cells2023

    • Author(s)
      Xiaoyan Ren, Gabriel Felipe Martinez-Galvez, Knut Woltjen
    • Organizer
      第3回研究交流サロン
    • Related Report
      2023 Annual Research Report
  • [Presentation] Discovery and generation of polymorphic copy number variants in human induced Pluripotent Stem cells2023

    • Author(s)
      Xiaoyan Ren, Gabriel Felipe Martinez-Galvez, Knut Woltjen
    • Organizer
      CiRA International Symposium 2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Limiting Cas9 accessibility within repetitive DNA generates polymorphic copy-number variants in iPS cells2023

    • Author(s)
      Gabriel Felipe Martinez-Galvez, Xiaoyan Ren, Knut Woltjen
    • Organizer
      日本分子生物学会第46回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Genome Editing in Human iPS Cells for Modeling Infectious and Genetic Disease2023

    • Author(s)
      Knut Woltjen
    • Organizer
      2023 Till & McCulloch Meetings
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genome Editing in Human iPS Cells for Modeling Infectious and Genetic Disease2023

    • Author(s)
      Knut Woltjen
    • Organizer
      国際キャリア基礎と実践
    • Related Report
      2023 Annual Research Report
  • [Presentation] Limiting Cas9 accessibility within repetitive DNA generates polymorphic copy-number variants in iPS cells2023

    • Author(s)
      Gabriel Felipe Martinez-Galvez, Knut Woltjen
    • Organizer
      2023 Till & McCulloch Meetings
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2023-04-26   Modified: 2024-12-25  

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