Liang Puping, Zhang Xiya, Chen Yuxi, Huang Junjiu
Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Reproductive Medicine of G uangdong Province, The Third Affiliated Hospital, Guangzhou Medical University and School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
J Gene Med. 2017 Jun;19(6-7). doi: 10.1002/jgm.2963.
Genome-editing tools are programmable artificial nucleases, mainly including zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeat (CRISPR). By recognizing and cleaving specific DNA sequences, genome-editing tools make it possible to generate site-specific DNA double-strand breaks (DSBs) in the genome. DSBs will then be repaired by either error-prone nonhomologous end joining or high-fidelity homologous recombination mechanisms. Through these two different mechanisms, endogenous genes can be knocked out or precisely repaired/modified. Rapid developments in genome-editing tools, especially CRISPR, have revolutionized human disease models generation, for example, various zebrafish, mouse, rat, pig, monkey and human cell lines have been constructed. Here, we review the developmental history of CRISPR and its application in studies of human diseases. In addition, we also briefly discussed the therapeutic application of CRISPR in the near future.
基因组编辑工具是可编程的人工核酸酶，主要包括锌指核酸酶、转录激活样效应因子核酸酶和成簇规律间隔短回文重复序列（CRISPR）。通过识别和切割特定的DNA序列，基因组编辑工具使得在基因组中产生位点特异性DNA双链断裂（DSB）成为可能。然后，DSB将通过易出错的非同源末端连接或高保真同源重组机制进行修复。通过这两种不同的机制，可以敲除内源基因或进行精确修复/修饰。基因组编辑工具，尤其是CRISPR的迅速发展，彻底改变了人类疾病模型的构建，例如，已经构建了各种斑马鱼、小鼠、大鼠、猪、猴和人类细胞系。在此，我们综述了CRISPR的发展历史及其在人类疾病研究中的应用。此外，我们还简要讨论了CRISPR在不久的将来的治疗应用。
