School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, 89154, USA.
Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV, 89154, USA.
Bioessays. 2019 Dec;41(12):e1900126. doi: 10.1002/bies.201900126. Epub 2019 Nov 6.
Genome editing with engineered nucleases (GEENs) introduce site-specific DNA double-strand breaks (DSBs) and repairs DSBs via nonhomologous end-joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical- or alternative-NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w.
基因组编辑与工程化核酸酶(GEENs)可引入特定的 DNA 双链断裂(DSB),并通过非同源末端连接(NHEJ)途径修复 DSB,最终在基因组中产生插入/缺失(indels)。有人询问基因编辑产生的 indels 的特征是否可以定制。对文献的回顾揭示了 NHEJ 途径的基因编辑技术如何影响基因编辑。该调查整合了大量文献,表明不同的 GEENs 和通过操纵关键 NHEJ 基因的表达,可以在一定程度上定制 indel 编辑的类型(插入、缺失和复杂)和大致长度。结构数据表明,GEENs 与 DNA 的结合可能会干扰 DNA 修复复合物关键成分的结合,有利于经典或替代 NHEJ。这些假设存在一些局限性,但如果得到验证,将使科学家能够更好地控制 indel 的组成,为基因编辑的基础科学和临床应用带来希望。另请在此处观看视频摘要:https://youtu.be/vTkJtUsLi3w。