The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.
The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.
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DOI：
10.1016/j.dnarep.2016.05.001
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发表时间：
2016-08
期刊：
影响因子：
3.8
通讯作者：
Haber JE
中科院分区：
文献类型：
--
作者：
Jasin M;Haber JE
DNA双链断裂(DSB)是一种危险的损伤，如果修复不当，可能会导致基因组变化或细胞死亡。生物体已经发展了几条修复DSB的途径，并有许多致力于修复DSB的因子，这种修复广泛地通过依赖于模板修复的相同或同源序列的同源重组或非同源末端连接来发生。我们对这些修复机制的大部分了解来自于对位点特异性核酸内切酶诱导DNA切割的研究。除了它们的生物学作用外，这些细胞途径还可以被用于基因编辑，以研究基因功能，或者用于基因治疗或其他应用。虽然第一次基因编辑实验是在20多年前进行的，但最近发现的RNA引导的内切酶简化了多年来开发的方法，使基因编辑成为整个生物医学研究界可用的方法。在这里，我们回顾了DSB修复机制和位点特异性切割系统，这些机制提供了对这些机制的见解，并导致了当前的基因编辑革命。
DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occur by homologous recombination that relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution.
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