中文摘要：

对基因组进行精确而有效的编辑修饰是生物学领域的重要探索内容。传统的基因操作手段由于效率、精确度低等问题，严重滞后于基因组研究的进展。近年来，新发展的基因编辑方法如锌指核酸酶（zinc finger nuclease,ZFN）、转录激活子样效应因子核酸酶（transcription activator-like effector nuclease,TALEN）和成簇规律间隔的短回文重复序列（clustered regularly interspaced short palindromic repeats,，CRISPR／cas9）等通过特异性识别和切割基因组DNA序列，可以诱发同源重组或非同源末端链接，使基因编辑更灵活、高效，从而开启了生物学研究及人类疾病机制研究新的模式。这三种基因编辑工具能够在不同的生物体及细胞中有效、特异地实现基因修饰，尤其是在干细胞中的应用，为人类疾病的机制研究及治疗带来了极大的便利和潜能。本文主要介绍ZFN、TALEN和CRISPR／Cas9方法的工作机制及其在人类疾病模型建立及基因治疗中的应用，同时展望了其未来的发展方向。

英文摘要：

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.