锌指核酸酶技术：遗传疾病建模与治疗中的进展与障碍

Zinc finger nuclease technology: advances and obstacles in modelling and treating genetic disorders.

作者信息

Jabalameli Hamid Reza, Zahednasab Hamid, Karimi-Moghaddam Amin, Jabalameli Mohammad Reza

机构信息

School of Veterinary Medicine, Azad University of Shahrekord, Shahrekord, Iran.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

出版信息

Gene. 2015 Mar 1;558(1):1-5. doi: 10.1016/j.gene.2014.12.044. Epub 2014 Dec 20.

DOI:10.1016/j.gene.2014.12.044

PMID:25536166

Abstract

Zinc finger nucleases (ZFNs) are engineered restriction enzymes designed to target specific DNA sequences within the genome. Assembly of zinc finger DNA-binding domain to a DNA-cleavage domain enables the enzyme machinery to target unique locus in the genome and invoke endogenous DNA repair mechanisms. This machinery offers a versatile approach in allele editing and gene therapy. Here we discuss the architecture of ZFNs and strategies for generating targeted modifications within the genome. We review advances in gene therapy and modelling of the disease using these enzymes and finally, discuss the practical obstacles in using this technology.

摘要

锌指核酸酶（ZFNs）是经过工程改造的限制性内切酶，旨在靶向基因组内的特定DNA序列。将锌指DNA结合结构域与DNA切割结构域组装在一起，可使酶机制靶向基因组中的独特位点，并激活内源性DNA修复机制。这种机制为等位基因编辑和基因治疗提供了一种通用方法。在此，我们讨论锌指核酸酶的结构以及在基因组内产生靶向修饰的策略。我们回顾了使用这些酶进行基因治疗和疾病建模的进展，最后讨论了使用该技术的实际障碍。