Generation of mutation-corrected induced pluripotent stem cell lines derived from adrenoleukodystrophy patient by using homology directed repair

Eul Sik Jung; Ji Hun Kim; Mi-Yoon Chang; Wonjun Hong; Zhejiu Quan; Seung Hyun Kim; Seungkwon You; Dae-Sung Kim; Jiho Jang; Sang-Hun Lee; Hyongbum Henry Kim; Hoon Chul Kang

doi:10.1016/j.scr.2022.102664

Generation of mutation-corrected induced pluripotent stem cell lines derived from adrenoleukodystrophy patient by using homology directed repair

Stem Cell Res. 2022 Mar:59:102664. doi: 10.1016/j.scr.2022.102664. Epub 2022 Jan 10.

Authors

Affiliations

¹ Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
² Division of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
³ Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea.
⁴ Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
⁵ Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, Republic of Korea.
⁶ Department of Physiology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁷ Division of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: HIPO0207@yuhs.ac.

PMID: 35042083
DOI: 10.1016/j.scr.2022.102664

Abstract

X-linked adrenoleukodystrophy (ALD) caused by the ABCD1 mutation, is the most common inherited peroxisomal disease. Previously, we generated an ALD patient-derived SCHi001-A iPSC model. In this study, we have performed the first genome editing of ALD patient-derived SCHi001-A iPSCs using homology-directed repair (HDR). The mutation site, c.1534G > A [GenBank: NM_000033.4], was corrected by introducing ssODN and the CRISPR/Cas9 system. The cell line exhibited normal iPSC plulipotency marker expression following genome editing. Mutation-corrected iPSCs from SCHi001-A iPSC line can be used in research into the pathophysiology of and therapeutics for ALD.

Keywords: CRISPR/Cas9; Genome editing; Induced pluripotent stem cell; X-linked adrenoleukodystrophy.