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Recent developments and clinical studies utilizing engineered zinc finger nuclease technology

Title
 Recent developments and clinical studies utilizing engineered zinc finger nuclease technology 
Authors
 Young-Il Jo ; Hyongbum Kim ; Suresh Ramakrishna 
Issue Date
2015
Journal Title
 Cellular and Molecular Life Sciences 
ISSN
 1420-682X 
Citation
 Cellular and Molecular Life Sciences, Vol.72(20) : 3819~3830, 2015 
Abstract
Efficient methods for creating targeted genetic modifications have long been sought for the investigation of gene function and the development of therapeutic modalities for various diseases, including genetic disorders. Although such modifications are possible using homologous recombination, the efficiency is extremely low. Zinc finger nucleases (ZFNs) are custom-designed artificial nucleases that make double-strand breaks at specific sequences, enabling efficient targeted genetic modifications such as corrections, additions, gene knockouts and structural variations. ZFNs are composed of two domains: (i) a DNA-binding domain comprised of zinc finger modules and (ii) the FokI nuclease domain that cleaves the DNA strand. Over 17 years after ZFNs were initially developed, a number of improvements have been made. Here, we will review the developments and future perspectives of ZFN technology. For example, ZFN activity and specificity have been significantly enhanced by modifying the DNA-binding domain and FokI cleavage domain. Advances in culture methods, such as the application of a cold shock and the use of small molecules that affect ZFN stability, have also increased ZFN activity. Furthermore, ZFN-induced mutant cells can be enriched using episomal surrogate reporters. Additionally, we discuss several ongoing clinical studies that are based on ZFN-mediated genome editing in humans. These breakthroughs have substantially facilitated the use of ZFNs in research, medicine and biotechnology.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/141471
DOI
10.1007/s00018-015-1956-5.
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
Yonsei Authors
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Link
 http://link.springer.com/article/10.1007%2Fs00018-015-1956-5
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