Gene editing of iPS cells derived from patients with congenital phagocytic disorders

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293231
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Masao 広島大学, 医歯薬保健学研究院, 教授 (00162016)
• Co-Investigator(Kenkyū-buntansha): Tsumura Miyuki 広島大学, 大学院医歯薬保健学研究院, 研究員 (80646274) ; Okada Satoshi 広島大学, 大学院医歯薬保健学研究院, 講師 (80457241) ; Yamamoto Takashi 広島大学, 大学院理学研究科, 教授 (90244102) ; Nakamura Kazuhiro 広島大学, 大学院医歯薬保健学研究院, 准教授 (70363059)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 先天性好中球減少症 / iPS細胞 / 遺伝子編集 / 人工ヌクレアーゼ

Outline of Final Research Achievements

This study demonstrated the establishment of the disease-specific iPS cells from patients with severe congenital neutropenia (SCN). Differentiation of myeloid cells derived from SCN-iPS cells was defected at the level of promyelocyte and myelocyte. This defect observed in iPS cells was similar finding shown in bone marrow of SCN patients. The mutation of ELANE identified in an SCN patient were corrected by gene-editing method using TALEN. The iPS cells edited were completely differentiated to mature neutrophils, suggesting the restoration of neutropenia in SCN patients. These results suggest that disease-specific iPS cells from patients with SCN may be useful to analyze the pathogenesis of the defect of myeloid differentiation, and that the possible restoration of ELANE mutation by gene-editing method using TALEN may result in the normal myeloid differentiation of neutrophils in iPS cells.

Free Research Field

小児科学，血液学，免疫学