Zinc-Finger Nucleases for Somatic Gene Therapy: The Next Frontier
Zinc-Finger Nucleases for Somatic Gene Therapy: The Next Frontier
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DOI：
10.1089/hum.2011.087
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发表时间：
2011-08-01
影响因子：
4.2
通讯作者：
Cathomen, Toni
中科院分区：
文献类型：
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作者：
Rahman, Shamim H.;Maeder, Morgan L.;Cathomen, Toni
锌指核酸酶（ZFN）是一种强大的工具，可用于编辑人类基因组的自由。在过去的几年中，该技术在靶位点特异性和用于产生锌指蛋白的工程平台方面都经历了显着的发展。因此，两个I期临床试验已经启动，旨在敲除从HIV患者分离的T细胞中的CCR5受体，以保护这些淋巴细胞免受病毒感染。此外，ZFN已成功地用于敲除或校正人类干细胞（包括造血前体细胞和诱导多能干细胞）中的疾病相关基因。在多能和多能干细胞中的靶向基因组工程方法为未来的策略提供了巨大的希望，这些策略旨在纠正先天性突变，以实现个性化的细胞替代疗法。本文综述了ZFN如何应用于基因治疗模型，讨论了与这种新技术相关的机会和风险，并提出了其在治疗性基因组工程中安全应用的未来方向。
Zinc-finger nucleases (ZFNs) are a powerful tool that can be used to edit the human genome ad libitum. The technology has experienced remarkable development in the last few years with regard to both the target site specificity and the engineering platforms used to generate zinc-finger proteins. As a result, two phase I clinical trials aimed at knocking out the CCR5 receptor in T cells isolated from HIV patients to protect these lymphocytes from infection with the virus have been initiated. Moreover, ZFNs have been successfully employed to knockout or correct disease-related genes in human stem cells, including hematopoietic precursor cells and induced pluripotent stem cells. Targeted genome engineering approaches in multipotent and pluripotent stem cells hold great promise for future strategies geared toward correcting inborn mutations for personalized cell replacement therapies. This review describes how ZFNs have been applied to models of gene therapy, discusses the opportunities and the risks associated with this novel technology, and suggests future directions for their safe application in therapeutic genome engineering.