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

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:
 [1] ;  [2] ;  [3] ;  [1] ;  [4]
  1. University of Bridgeport, Biomedical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA
  2. Physics Faculty, BHSEC Queens, 30-20 Thomson Avenue, Long Island City, NY 11101, USA
  3. University of Bridgeport, Mechanical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA
  4. University of Bridgeport, Electrical Engineering, 221 University Avenue, Bridgeport, CT 06604, USA
Publication Date:
OSTI Identifier:
1209764
Grant/Contract Number:
AC02-98CH10886
Type:
Published Article
Journal Name:
Biotechnology Research International
Additional Journal Information:
Journal Volume: 2014; Related Information: CHORUS Timestamp: 2016-07-29 07:56:50; Journal ID: ISSN 2090-3138
Publisher:
Hindawi Publishing Corporation
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
Country unknown/Code not available
Language:
English