한빛사 논문
Seonghyun Lee1†, Hyunji Lee2,3†, Gayoung Baek1, Eunji Namgung4, Joo Min Park4, Sanghun Kim2,5, Seongho Hong2 and Jin‑Soo Kim1*
1 Center for Genome Engineering, Institute for Basic Science, Daejeon 34126, Republic of Korea
2 Laboratory Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea
3 School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea
4 Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Republic of Korea
5 College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
†Seonghyun Lee and Hyunji Lee contributed equally to this work.
*Correspondence: Jin‑Soo Kim
Abstract
We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.
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