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Lee, Hyun Ji
유전체 교정 연구단
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Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases

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Title
Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases
Author(s)
Hyunji Lee; Seonghyun Lee; Gayoung Baek; Annie Kim; Beum-Chang Kang; Huiyun Seo; Jin-Soo Kim
Publication Date
2021-12
Journal
NATURE COMMUNICATIONS, v.12, no.1
Publisher
NATURE RESEARCH
Abstract
DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA(tox), transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders. Split DddA-derived base editors fused to TALEs enable mitochondrial DNA editing. Here the authors demonstrate their use in mouse embryos with germline transmission.
URI
https://pr.ibs.re.kr/handle/8788114/9498
DOI
10.1038/s41467-021-21464-1
ISSN
2041-1723
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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