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2015 ; 116
(11
): 2435-44
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gab.com Text
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English Wikipedia
Artificial zinc finger DNA binding domains: versatile tools for genome
engineering and modulation of gene expression
#MMPMID25989233
Hossain MA
; Barrow JJ
; Shen Y
; Haq MI
; Bungert J
J Cell Biochem
2015[Nov]; 116
(11
): 2435-44
PMID25989233
show ga
Genome editing and alteration of gene expression by synthetic DNA binding
activities gained a lot of momentum over the last decade. This is due to the
development of new DNA binding molecules with enhanced binding specificity. The
most commonly used DNA binding modules are zinc fingers (ZFs), TALE-domains, and
the RNA component of the CRISPR/Cas9 system. These binding modules are fused or
linked to either nucleases that cut the DNA and induce DNA repair processes, or
to protein domains that activate or repress transcription of genes close to the
targeted site in the genome. This review focuses on the structure, design, and
applications of ZF DNA binding domains (ZFDBDs). ZFDBDs are relatively small and
have been shown to penetrate the cell membrane without additional tags suggesting
that they could be delivered to cells without a DNA or RNA intermediate. Advanced
algorithms that are based on extensive knowledge of the mode of ZF/DNA
interactions are used to design the amino acid composition of ZFDBDs so that they
bind to unique sites in the genome. Off-target binding has been a concern for all
synthetic DNA binding molecules. Thus, increasing the specificity and affinity of
ZFDBDs will have a significant impact on their use in analytical or therapeutic
settings.