Journal
GENE THERAPY
Volume 19, Issue 4, Pages 458-462Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2011.112
Keywords
gene switch; zinc finger; transcription factor; benzoate X receptor; nuclear receptor
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Funding
- National Institute of Health [R01GM065059]
- American Cancer Society Illinois Division
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Targeted zinc-finger (ZF) DNA-binding domains in conjunction with nuclear receptor ligand-binding domains (LBDs) produce chemically inducible gene switches that have applications in gene therapy and proteomic and genomic research. The benzoate X receptor-beta (BXR beta) LBD was used to construct homodimer and single-chain ZF transcription factors (ZF(TF)s). These ZF(TF)s specifically regulated the transcription of target genes in response to two ligands, ethyl-4-hydroxybenzoate and propyl-4-hydroxybenzoate, in a dose-dependent manner. The ZF(TF)s also regulated the expression of endogenous intercellular adhesion molecule-1 in response to either ligand. The advantage of BXR beta-based ZF(TF)s is that the ligands are inexpensive and easily synthetically modified, making the system a base for creation of orthogonal ligand-receptor pairs and expanding the gene-switch toolbox. Gene Therapy (2012) 19, 458-462; doi: 10.1038/gt.2011.112; published online 28 July 2011
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