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Alterations in mitochondrial base editors enhance targeted editing efficiency for mouse model generation

Authors
 Seongho Hong  ;  Sol Pin Kim  ;  Sanghun Kim  ;  Soo Kyung Kang  ;  Sungmo Jung  ;  Yeji Oh  ;  Seung Hee Choi  ;  Su Bin Lee  ;  Hou Cha  ;  Jieun Kim  ;  Jiyoung Bae  ;  Jiyoon Park  ;  Kyoungmi Kim  ;  Chang Geun Choi  ;  Soo-Ji Park  ;  Do Hyun Kim  ;  Lark Kyun Kim  ;  Je Kyung Seong  ;  Hyunji Lee 
Citation
 MOLECULAR THERAPY-NUCLEIC ACIDS, Vol.36(3) : 102678, 2025-09 
Journal Title
MOLECULAR THERAPY-NUCLEIC ACIDS
Issue Date
2025-09
MeSH
0
Abstract
MT: RNA/DNA Editing; TALED; base editing; mitochondria; mitochondrial editing; mtDNA
Article Number
 10.1016/j.omtn.2025.102678 
DOI
Mitochondrial DNA (mtDNA) base editors are powerful tools for investigating mitochondrial diseases. However, their editing efficiency can vary significantly depending on the target site within the mtDNA. In this study, we developed two improved versions of the mitochondrial adenine base editor (Hifi-sTALED and αnHifi-sTALED) by modifying components other than the TadA8e-V28R deaminase variant. These enhancements significantly increased editing efficiency while preserving minimal off-target effects across the transcriptome. Using these optimized editors, we achieved improved mtDNA editing in mouse embryos and successfully generated mt-Rnr1 mutant mice with high heteroplasmic loads. Functional analyses revealed that the mt-Rnr1 mutation impaired mitochondrial function, as indicated by reduced ATP production and decreased oxygen consumption rate (OCR). These findings demonstrate the utility of the enhanced base editors in generating mitochondrial disease models and advancing research in mitochondrial genetics.
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Lark Kyun(김락균) ORCID logo https://orcid.org/0000-0001-5983-4470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/207417
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