Table of Contents
Biotechnology Research International
Volume 2014 (2014), Article ID 970595, 27 pages
http://dx.doi.org/10.1155/2014/970595
Research Article

Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

1University of Bridgeport, Biomedical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA
2Physics Faculty, BHSEC Queens, 30-20 Thomson Avenue, Long Island City, NY 11101, USA
3University of Bridgeport, Mechanical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA
4University of Bridgeport, Electrical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA

Received 13 September 2013; Revised 2 January 2014; Accepted 2 January 2014; Published 6 April 2014

Academic Editor: Michael Hust

Copyright © 2014 Christian Bach et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable tools to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.