dystrophic epidermolysis bullosaopen access
- Authors
- Hong, Sung-Ah; Kim, Song-Ee; Lee, A-Young; Hwang, Gue-Ho; Kim, Jong Hoon; Iwata, Hiroaki; Kim, Soo-Chan; Bae, Sangsu; Lee, Sang Eun
- Issue Date
- Aug-2022
- Publisher
- CELL PRESS
- Keywords
- base editing; COL7A1; CRISPR; genome editing; prime editing; recessive dystrophic epidermolysis bullosa; type VII collagen
- Citation
- MOLECULAR THERAPY, v.30, no.8, pp.2664 - 2679
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR THERAPY
- Volume
- 30
- Number
- 8
- Start Page
- 2664
- End Page
- 2679
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172588
- DOI
- 10.1016/j.ymthe.2022.06.005
- ISSN
- 1525-0016
- 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.
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