期刊
ACS SYNTHETIC BIOLOGY
卷 8, 期 4, 页码 621-632出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.8b00411
关键词
mito-CRISPR/Cas9; mitochondria; mtDNA editing; ssDNA; zebrafish
资金
- CAS Team Project of the Belt and Road
- Three Hundred Leading Talents in Scientific and Technological Innovation Program of Chongqing [CSTCCXLJRC201714]
- Program of China -Sri Lanka Joint Research and Demonstration Center for Water Technology
The mitochondria DNA (mtDNA) editing tool, zinc finger nucleases (ZFNs), transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system, is a promising approach for the treatment of mtDNA diseases by eliminating mutant mitochondrial genomes. However, there have been no reports of repairing the mutant mtDNA with homologous recombination strategy to date. Here, we show a mito-CRISPR/Cas9 system that mito-Cas9 protein can specifically target mtDNA and reduce mtDNA copy number in both human cells and zebrafish. An exogenous single-stranded DNA with short homologous arm was knocked into the targeting loci accurately, and this mutagenesis could be steadily transmitted to F-1 generation of zebrafish. Moreover, we found some major factors involved in nuclear DNA repair were upregulated significantly by the mito-CRISPR/Cas9 system. Taken together, our data suggested that the mito-CRISPR/Cas9 system could be a useful method to edit mtDNA by knock-in strategy, providing a potential therapy for the treatment of inherited mitochondrial diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据