Dion Sarah, Demattéi Marie-Véronique, Renault Sylvaine
Laboratoire d'Etude des Parasites Génétiques, FRE CNRS 2969, Université François Rabelais, Parc Grandmont, 37270 Tours, France.
Med Sci (Paris). 2007 Oct;23(10):834-9. doi: 10.1051/medsci/20072310834.
The ability to achieve site-specific correction or modification of the genome has widespread implications for basic and applied research. Individual zinc finger (ZF) domain recognizes DNA triplets with high specificity and affinity. They are used to create zinc finger protein (ZFP), like the ZF-nucleases, which could be designed to be specific for nearly any site in the genome. These domains can be tandemly linked to recognize DNA sequences of different lengths, with high fidelity. Different methods have been developed to design ZF specifically targeted to any triplet. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA. By fusing ZF to repression or activation domains, genes can be selectively targeted and switched off and on. Zinc-finger proteins (ZFPs) that recognize novel DNA sequences are the basis of a powerful technology platform with many uses in therapeutics. The ZF have been used as the DNA-binding domains of novel transcription factors (ZFP TFs) which are used to inhibit or activate genes involved in different diseases. ZF-nucleases are developed to modify genes implicated in different diseases. Many clinical trials using ZFPs are currently under investigation.
实现基因组位点特异性校正或修饰的能力对基础研究和应用研究具有广泛影响。单个锌指(ZF)结构域能以高特异性和亲和力识别DNA三联体。它们被用于创建锌指蛋白(ZFP),如锌指核酸酶,其可被设计成对基因组中几乎任何位点具有特异性。这些结构域可以串联连接,以高保真度识别不同长度的DNA序列。已经开发出不同方法来设计特异性靶向任何三联体的锌指。这种模块化设计为DNA的特异性识别提供了大量组合可能性。通过将锌指与抑制或激活结构域融合,可以选择性地靶向基因并使其关闭和开启。识别新DNA序列的锌指蛋白(ZFP)是一个强大技术平台的基础,在治疗学中有许多用途。锌指已被用作新型转录因子(ZFP TF)的DNA结合结构域,用于抑制或激活与不同疾病相关的基因。锌指核酸酶被开发用于修饰与不同疾病相关的基因。目前许多使用锌指蛋白的临床试验正在进行研究。