Adenine base editing and prime editing of chemically derived hepatic progenitors rescue genetic liver disease
- Authors
- Kim, Yohan; Hong, Sung-Ah; Yu, Jihyeon; Eom, Jeongyun; Jang, Kiseok; Yoon, Sangtae; Hong, Da Hee; Seo, Daekwan; Lee, Seu-Na; Woo, Jae-Sung; Jeong, Jaemin; Bae, Sangsu; Choi, Dongho
- Issue Date
- 2-9월-2021
- Publisher
- CELL PRESS
- Keywords
- adenine base editor; chemically derived hepatic progenitor; ex vivo gene editing therapy; genetic disorder; prime editing; regenerative medicine; reprogramming; tyrosinemia type 1
- Citation
- CELL STEM CELL, v.28, no.9, pp.1614 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL STEM CELL
- Volume
- 28
- Number
- 9
- Start Page
- 1614
- End Page
- +
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/136391
- DOI
- 10.1016/j.stem.2021.04.010
- ISSN
- 1934-5909
- Abstract
- DNA base editors and prime editing technology enable therapeutic in situ correction of disease-causing alleles. These techniques could have broad applications for ex vivo editing of cells prior to transplantation in a range of diseases, but it is critical that the target population is efficiently modified and engrafts into the host. Chemically derived hepatic progenitors (CdHs) are a multipotent population capable of robust engraftment and hepatocyte differentiation. Here we reprogrammed hepatocytes from a mouse model of hereditary tyrosinemia type 1 (HT1) into expandable CdHs and successfully corrected the disease-causing mutation using both adenine base editors (ABEs) and prime editors (PEs). ABE- and PE-corrected CdHs repopulated the liver with fumarylacetoacetate hydrolase-positive cells and dramatically increased survival of mutant HT1 mice. These results demonstrate the feasibility of precise gene editing in transplantable cell populations for potential treatment of genetic liver disease.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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