In vivo gene editing via homology-independent targeted integration for adrenoleukodystrophy treatment

Sung Ah Hong, Jung Hwa Seo, Soohyun Wi, Eul Sik Jung, Jihyeon Yu, Gue Ho Hwang, Ji Hea Yu, Ahreum Baek, Soeon Park, Sangsu Bae, Sung Rae Cho

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Adrenoleukodystrophy (ALD) is caused by various pathogenic mutations in the X-linked ABCD1 gene, which lead to metabolically abnormal accumulations of very long-chain fatty acids in many organs. However, curative treatment of ALD has not yet been achieved. To treat ALD, we applied two different gene-editing strategies, base editing and homology-independent targeted integration (HITI), in ALD patient-derived fibroblasts. Next, we performed in vivo HITI-mediated gene editing using AAV9 vectors delivered via intravenous administration in the ALD model mice. We found that the ABCD1 mRNA level was significantly increased in HITI-treated mice, and the plasma levels of C24:0-LysoPC (lysophosphatidylcholine) and C26:0-LysoPC, sensitive diagnostic markers for ALD, were significantly reduced. These results suggest that HITI-mediated mutant gene rescue could be a promising therapeutic strategy for human ALD treatment.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalMolecular Therapy
Issue number1
Publication statusPublished - 2022 Jan 5

Bibliographical note

Funding Information:
We thank Prof. Hyongbum (Henry) Kim for helpful comments during this study. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea ( HI16C1012 to S.B. and S.-R.C.) and the Bio & Medical Technology Development Program of the National Research Foundation ( 2020M3A9I4036072 to S.B.).

Publisher Copyright:
© 2021 The American Society of Gene and Cell Therapy

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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