[Applications of ZFN, TALEN and CRISPR/Cas9 techniques in disease modeling and gene therapy].
[Applications of ZFN, TALEN and CRISPR/Cas9 techniques in disease modeling and gene therapy].
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DOI：
10.3760/cma.j.issn.1003-9406.2016.06.025
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Guohua Zhao;J. Pu;B. Tang
中科院分区：
文献类型：
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作者：
Guohua Zhao;J. Pu;B. Tang
精确而有效地修饰预测基因座上的复杂基因组一直是科学家们的重要目标。然而，在不同的生物和细胞中操纵基因组的传统技术已经落后于基因组研究的快速发展。这种基因组工程工具的特点是效率低，目标不明确。新开发的定制设计的核酸酶、锌指核酸酶(ZFN)、转录激活物样效应核酸酶(TALEN)和规则间隔短回文重复序列(CRISPR)/CRISPR相关(CAS)系统使基因组修饰变得容易定制、灵活和高效，这可能会影响生物学研究和人类疾病发病机制的研究。这些新技术可以在包括诱导多能干细胞(IPSCs)在内的多种生物和细胞类型中高效和特异地编辑基因组DNA，这使它们有可能揭示许多人类疾病的发病机制和治疗。本文简要介绍了ZFN、TALENS和CRISPR/CAS9系统的作用机制，并比较了这些方法的有效性和特异性。此外，还讨论了ZFN、TALENS和CRISPR/Cas9介导的基因组修饰在人类疾病模型和基因治疗中的应用。
Precise and effective modification of complex genomes at the predicted loci has long been an important goal for scientists. However, conventional techniques for manipulating genomes in diverse organisms and cells have lagged behind the rapid advance in genomic studies. Such genome engineering tools have featured low efficiency and off-targeting. The newly developed custom-designed nucleases, zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system have conferred genome modification with ease of customization, flexibility and high efficiency, which may impact biological research and studies on pathogenesis of human diseases. These novel techniques can edit the genomic DNA with high efficiency and specificity in a rich variety of organisms and cell types including the induced pluripotent stem cells (iPSCs), which has conferred them with the potential for revealing the pathogenesis and treatment of many human diseases. This review has briefly introduced the mechanisms of ZFN, TALENs and CRISPR/Cas9 system, and compared the efficiency and specificity of such approaches. In addition, the application of ZFN, TALENs and CRISPR/Cas9 mediated genome modification for human disease modeling and gene therapy was also discussed.