Department of Molecular Diagnostics and Biopharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
Mol Biotechnol. 2013 Sep;55(1):54-62. doi: 10.1007/s12033-012-9613-9.
The development of engineered nucleases is the fruit of a new technological approach developed in the last two decades which has led to significant benefits on genome engineering, particularly on gene therapy. These applications enable efficient and specific genetic modifications via the induction of a double-strand break (DSB) in a specific genomic target sequence, followed by the homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. In addition to the application on gene modification in cells and intact organisms, a number of recent papers have reported that this gene editing technology can be applied effectively to human diseases. With the promising data obtained using engineered endonucleases in gene therapy, it appears reasonable to expect that more diseases could be treated and even be cured in this new era of individualized medicine. This paper first brief introduces the development of engineered nucleases with a special emphasis on zinc-finger nucleases (ZFNs) and transcription activator-like effector (TALE) nucleases (TALENs), and then takes CCR5-based gene therapy as an example to discuss the therapeutic applications of engineered nucleases.
工程化核酸酶的发展是过去二十年中开发的新技术方法的成果，它在基因组工程方面带来了重大益处，特别是在基因治疗方面。这些应用通过在特定基因组靶序列中诱导双链断裂（DSB），随后通过同源定向修复（HDR）或非同源末端连接（NHEJ）途径，实现了高效和特异性的基因修饰。除了在细胞和完整生物体中的基因修饰应用外，最近的一些论文还报告了这种基因编辑技术可以有效地应用于人类疾病。鉴于在基因治疗中使用工程化内切酶获得的有前景的数据，似乎可以合理地期望在个体化医学的新时代，更多的疾病可以得到治疗甚至治愈。本文首先特别介绍了工程化核酸酶的发展，重点介绍了锌指核酸酶（ZFNs）和转录激活因子样效应物（TALE）核酸酶（TALENs），然后以基于 CCR5 的基因治疗为例，讨论了工程化核酸酶的治疗应用。
