한빛사논문
Jin-Soo Kim 1,2,* & Jia Chen 3,4,*
1NUS Synthetic Biology for Clinical & Technological Innovation (SynCTI) and Department of Biochemistry, National University of Singapore, Singapore, Singapore.
2Edgene, Seoul, South Korea.
3Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
4Shanghai Clinical Research and Trial Center, Shanghai, China.
*Corresponding authors: correspondence to Jin-Soo Kim or Jia Chen
Abstract
Mitochondria and chloroplasts are organelles that include their own genomes, which encode key genes for ATP production and carbon dioxide fixation, respectively. Mutations in mitochondrial DNA can cause diverse genetic disorders and are also linked to ageing and age-related diseases, including cancer. Targeted editing of organellar DNA should be useful for studying organellar genes and developing novel therapeutics, but it has been hindered by lack of efficient tools in living cells. Recently, CRISPR-free, protein-only base editors, such as double-stranded DNA deaminase toxin A-derived cytosine base editors (DdCBEs) and adenine base editors (ABEs), have been developed, which enable targeted organellar DNA editing in human cell lines, animals and plants. In this Review, we present programmable deaminases developed for base editing of organellar DNA in vitro and discuss mitochondrial DNA editing in animals, and plastid genome (plastome) editing in plants. We also discuss precision and efficiency limitations of these tools and propose improvements for therapeutic, agricultural and environmental applications.
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