김송이 (연세대학교 의과대학) | 한빛사논문 > 한빛사

한빛사논문

조회465

연세대학교 의과대학

CV File 135 kb

Mol. Ther., Volume 30, Issue 8, 3 August 2022, Pages 2664-2679 | https://doi.org/10.1016/j.ymthe.2022.06.005 Therapeutic base editing and prime editing of COL7A1 mutations in recessive dystrophic epidermolysis bullosa

Sung-Ah Hong^1,7, Song-Ee Kim^2,7, A-Young Lee², Gue-Ho Hwang³, Jong Hoon Kim², Hiroaki Iwata⁴, Soo-Chan Kim⁵, Sangsu Bae^1,6, Sang Eun Lee²

¹Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, South Korea
²Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 06273, South Korea
³Department of Chemistry, Hanyang University, Seoul 04763, South Korea
⁴Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
⁵Department of Dermatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, South Korea
⁶Department of Biomedical Sciences, Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, South Korea

⁷These authors contributed equally
Corresponding authors: Sangsu Bae,Sang Eun Lee

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by loss-of-function mutations in the COL7A1 gene, which encodes type VII collagen (C7), a protein that functions in skin adherence. From 36 Korean RDEB patients, we identified a total of 69 pathogenic mutations (40 variants without recurrence), including point mutations (72.5%) and insertion/deletion mutations (27.5%). For fibroblasts from two patients (Pat1 and Pat2), we applied adenine base editors (ABEs) to correct the pathogenic mutation of COL7A1 or to bypass a premature stop codon in Pat1-derived primary fibroblasts. To expand the targeting scope, we also utilized prime editors (PEs) to correct the COL7A1 mutations in Pat1- and Pat2-derived fibroblasts. Ultimately, we found that transfer of edited patient-derived skin equivalents (i.e., RDEB keratinocytes and PE-corrected RDEB fibroblasts from the RDEB patient) into the skin of immunodeficient mice led to C7 deposition and anchoring fibril formation within the dermal-epidermal junction, suggesting that base editing and prime editing could be feasible strategies for ex vivo gene editing to treat RDEB.

논문정보

형식Research article
게재일2022년 08월 (BRIC 등록일 2022-10-17)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생화학

댓글 작성 로그인

CV 열람하기

연락처 보기