当前位置: X-MOL 学术Nat. Rev. Mol. Cell Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Base editing of organellar DNA with programmable deaminases
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date : 2023-10-04 , DOI: 10.1038/s41580-023-00663-2
Jin-Soo Kim 1, 2 , Jia Chen 3, 4
Affiliation  

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.



中文翻译:

使用可编程脱氨酶对细胞器 DNA 进行碱基编辑

线粒体和叶绿体是包含自己基因组的细胞器,分别编码用于 ATP 生成和二氧化碳固定的关键基因。线粒体 DNA 突变可导致多种遗传性疾病,也与衰老和与年龄相关的疾病(包括癌症)有关。细胞器 DNA 的靶向编辑应该有助于研究细胞器基因和开发新的治疗方法,但由于活细胞中缺乏有效的工具而受到阻碍。最近,开发了无 CRISPR、仅蛋白质的碱基编辑器,例如双链 DNA 脱氨酶毒素 A 衍生的胞嘧啶碱基编辑器 (DdCBE) 和腺嘌呤碱基编辑器 (ABE),能够在人类细胞中进行靶向细胞器 DNA 编辑线条、动物和植物。在这篇综述中,我们介绍了为体外细胞器 DNA 碱基编辑而开发的可编程脱氨酶,并讨论了动物中的线粒体 DNA 编辑和植物中的质体基因组(质体组)编辑。我们还讨论了这些工具的精度和效率限制,并提出了治疗、农业和环境应用的改进方案。

更新日期:2023-10-04
down
wechat
bug