Correction of X-linked Neutropenia(XLN) by iPS cell based new gene modified therapy

• Project/Area Number: 18K16112
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: チャンダ ビディシャ 東京大学, 医科学研究所, 特任研究員 (70725358)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Discontinued (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: X-linked Neutropenia / iPS / Hematopoietic Stem cell / Gene Editing / X-Linked Neutropenia / Hematopoietic stem cells / Gene editing / Mouse model

Outline of Annual Research Achievements

In vivo XLN mouse model:
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disorder. Mutation in WAS gene cause Wiskott-Aldrich syndrome.We performed the whole genome sequencing of the blood cells from an XLN patient and identified a novel missense mutation in the WAS gene (WASp I290T).We used CRISPER/Cas9 system to generate knock in mouse model. We successfully knocked in I292T mutation in exan 9 of WAS gene in mice which was compatible of WAS I290T human mutation.As a result we got two mutation positive male and three female mice. Then cross breeding in between them to get pure homozygous mouse for this model system.

Research Products

• [Presentation] Functional analysis of the novel WASP mutation resulting in X-linked congenital neutropenia (2018)
  • Author(s): Masayuki Kobayashi,Chanda Bidisha,Muneyoshi Futami,,Mizuho Yamashita,Mitsuhiro Hirano,Kazuaki Yokoyama,Yoichi Imai, Eigo Yusa,Rui Yamaguchi,Seiya Imoto,Satoru Miyano,Arinobu Tojo
  • Organizer: 80th annual meeting of the JSH