DddA homolog search and engineering expand sequence compatibility of mitochondrial base editing

Li Mi, Ming Shi, Yu-Xuan Li, Gang Xie, Xichen Rao, Damu Wu, Aimin Cheng, Mengxiao Niu, Fengli Xu, Ying Yu, Ning Gao, Wensheng Wei, Xianhua Wang and Yangming Wang ()
Additional contact information
Li Mi: Peking University
Ming Shi: Peking University
Yu-Xuan Li: Peking University
Gang Xie: Peking University
Xichen Rao: Peking University
Damu Wu: Peking University
Aimin Cheng: Peking University
Mengxiao Niu: Peking University
Fengli Xu: Peking University
Ying Yu: Peking University
Ning Gao: Peking University
Wensheng Wei: Peking University
Xianhua Wang: Peking University
Yangming Wang: Peking University

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: Abstract Expanding mitochondrial base editing tools with broad sequence compatibility is of high need for both research and therapeutic purposes. In this study, we identify a DddA homolog from Simiaoa sunii (Ddd_Ss) which can efficiently deaminate cytosine in DC context in double-stranded DNA (dsDNA). We successfully develop Ddd_Ss-derived cytosine base editors (DdCBE_Ss) and introduce mutations at multiple mitochondrial DNA (mtDNA) loci including disease-associated mtDNA mutations in previously inaccessible GC context. Finally, by introducing a single amino acid substitution from Ddd_Ss, we successfully improve the activity and sequence compatibility of DdCBE derived from DddA of Burkholderia cenocepacia (DdCBE_Bc). Our study expands mtDNA editing tool boxes and provides resources for further screening and engineering dsDNA base editors for biological and therapeutic applications.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36600-2

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DOI: 10.1038/s41467-023-36600-2

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