김동민 (성균관대학교)

한빛사논문

조회299

김동민Dongmin Gim

성균관대학교

CV File 174 kb

Nucleic Acids Res., Apr 25 2024, gkae310 | https://doi.org/10.1093/nar/gkae310 Precise editing of pathogenic nucleotide repeat expansions in iPSCs using paired prime editor

Hye-Yeon Hwang ¹, Dongmin Gim ^2,3, Hwalin Yi¹, Hyewon Jung ², Jaecheol Lee ^2,3,4,5, Daesik Kim¹

¹Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.

²School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

³Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.

⁴Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea.

⁵Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.

The first two authors should be regarded as Joint First Authors.

Corresponding authors : Jaecheol Lee, Daesik Kim

Abstract

Nucleotide repeat expansion disorders, a group of genetic diseases characterized by the expansion of specific DNA sequences, pose significant challenges to treatment and therapy development. Here, we present a precise and programmable method called prime editor-mediated correction of nucleotide repeat expansion (PE-CORE) for correcting pathogenic nucleotide repeat expansion. PE-CORE leverages a prime editor and paired pegRNAs to achieve targeted correction of repeat sequences. We demonstrate the effectiveness of PE-CORE in HEK293T cells and patient-derived induced pluripotent stem cells (iPSCs). Specifically, we focus on spinal and bulbar muscular atrophy and spinocerebellar ataxia type, two diseases associated with nucleotide repeat expansion. Our results demonstrate the successful correction of pathogenic expansions in iPSCs and subsequent differentiation into motor neurons. Specifically, we detect distinct downshifts in the size of both the mRNA and protein, confirming the functional correction of the iPSC-derived motor neurons. These findings highlight PE-CORE as a precision tool for addressing the intricate challenges of nucleotide repeat expansion disorders, paving the way for targeted therapies and potential clinical applications.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-05-08)
연구진국내 연구진
분야 생명과학 > 유전학

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