한빛사 논문
Sung-Ik Cho,1,2 Seonghyun Lee,1 Young Geun Mok,1 Kayeong Lim,1 Jaesuk Lee,1,2 Ji Min Lee,1,2 Eugene Chung,1,2 and Jin-Soo Kim1,3,*
1Center for Genome Engineering, Institute for Basic Science, Daejeon 34126, Republic of Korea 2Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea 3Lead contact
*Correspondence
Abstract
Mitochondrial DNA (mtDNA) editing paves the way for disease modeling of mitochondrial genetic disorders in cell lines and animals and also for the treatment of these diseases in the future. Bacterial cytidine deaminase DddA-derived cytosine base editors (DdCBEs) enabling mtDNA editing, however, are largely limited to C-to-T conversions in the 5′-TC context (e.g., TC-to-TT conversions), suitable for generating merely 1/8 of all possible transition (purine-to-purine and pyrimidine-to-pyrimidine) mutations. Here, we present transcription-activator-like effector (TALE)-linked deaminases (TALEDs), composed of custom-designed TALE DNA-binding arrays, a catalytically impaired, full-length DddA variant or split DddA originated from Burkholderia cenocepacia, and an engineered deoxyadenosine deaminase derived from the E. coli TadA protein, which induce targeted A-to-G editing in human mitochondria. Custom-designed TALEDs were highly efficient in human cells, catalyzing A-to-G conversions at a total of 17 target sites in various mitochondrial genes with editing frequencies of up to 49%.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기