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

Table 7

Evolutionary traits to be considered or reused in the design of zinc finger domains.

Evolutionary trait	References and comments
Binding spectra	A single zinc finger binds many triplets[2, 3] related to Lam’s degeneracy
Condition dependency	Binding of dissimilar sequence in various conditions [1–3, 10, 11] and high failure rates of intended target site [7]
Context dependency	The interdependence between all fingers in a domain through the overlap loci [3, 8]
Sequence dependency	Form of DNA determines the binding sequence a domain can recognize [11] p. 242
Dynamic biological 3D malleability	Of the three-dimensional structure of single fingers and entire domains and the form and deformability of DNA structure [8, 11, 57]
Reversibility	Formation and dissolution of DNA-protein complex is an indispensable property of a functional regulatory network system
Evolutionary dualisms	Duality of conserving and changing gene and protein sequences [1] and reversibility of biological processes and functions [1, 2, 11, 57]
4th base overlap loci	Complex stabilization and dissolution loci to control the reversibility process [3],
Binding initiation: 1st finger of SP1	The 1st finger has unique evolutionary traits never detected in other fingers as well as relaxed binding specificity and affinity and therefore is likely to initiate complex formation [8].; The 1st finger’s condition dependency is unlike other fingers [58]