title: Evaluation of novel design strategies for developing zinc finger nucleases tools for treating human diseases.
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.
authors.affiliation: University of Bridgeport, Biomedical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Bach
authors.affiliation: Physics Faculty, BHSEC Queens, 30-20 Thomson Avenue, Long Island City, NY 11101, USA.
authors.forename: William
authors.initials: W
authors.lastname: Sherman
authors.affiliation: University of Bridgeport, Mechanical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA.
authors.forename: Jani
authors.initials: J
authors.lastname: Pallis
authors.affiliation: University of Bridgeport, Biomedical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA.
authors.forename: Prabir
authors.identifier: 0000-0002-2917-793X
authors.initials: P
authors.lastname: Patra
authors.affiliation: University of Bridgeport, Electrical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Bajwa