Recent developments and clinical studies utilizing engineered zinc finger nuclease technology

Title
Recent developments and clinical studies utilizing engineered zinc finger nuclease technology
Authors
Ramakrishna Suresh
Keywords
Farm animals; Pre-clinical trials; Programmable nucleases; Targeted genetic modifications; Therapeutic applications; ZFN architecture; ZFN delivery; ZFN modification
Issue Date
2015-06
Publisher
SPRINGER BASEL AG
Citation
CELLULAR AND MOLECULAR LIFE SCIENCES, v. 72, NO 20, Page. 3819-3830
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://link.springer.com/article/10.1007/s00018-015-1956-5http://hdl.handle.net/20.500.11754/25516
ISSN
1420-682X; 1420-9071
DOI
http://dx.doi.org/10.1007/s00018-015-1956-5
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Graduate School of Biomedical Science & Engineering[S](의생명공학전문대학원) > ETC
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