title: Artificial zinc finger DNA binding domains: versatile tools for genome engineering and modulation of gene expression.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Cancer Center, Genetics Institute, University of Florida, Gainesville, Florida, 32610.
authors.forename: Mir A
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Cancer Center, Genetics Institute, University of Florida, Gainesville, Florida, 32610.
authors.forename: Joeva J
authors.initials: JJ
authors.lastname: Barrow
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Cancer Center, Genetics Institute, University of Florida, Gainesville, Florida, 32610.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Cancer Center, Genetics Institute, University of Florida, Gainesville, Florida, 32610.
authors.forename: Md Imdadul
authors.initials: MI
authors.lastname: Haq
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Cancer Center, Genetics Institute, University of Florida, Gainesville, Florida, 32610.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bungert
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D008958:Models, Molecular; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA
keywords: genome editing; modulation of gene expression; synthetic DNA binding domain; zinc finger