ArticleGene therapy2000
The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.
Article in Gene therapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 55 citations in OpenAlex.
- Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies.Neuropathology and applied neurobiology · 2021Article
- Utrophin up-regulation by artificial transcription factors induces muscle rescue and impacts the neuromuscular junction in mdx mice.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- ZFP226 is a novel artificial transcription factor for selective activation of tumor suppressor KIBRA.Scientific reports · 2018Article
- Genome engineering: a new approach to gene therapy for neuromuscular disorders.Nature reviews. Neurology · 2017Review
- Current understanding of molecular pathology and treatment of cardiomyopathy in duchenne muscular dystrophy.Molecules (Basel, Switzerland) · 2015Review
- High throughput screening in duchenne muscular dystrophy: from drug discovery to functional genomics.Biology · 2014Review
- Novel adeno-associated viral vector delivering the utrophin gene regulator jazz counteracts dystrophic pathology in mdx mice.Journal of cellular physiology · 2014Article
- Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression.Methods (San Diego, Calif.) · 2014Article
- UtroUp is a novel six zinc finger artificial transcription factor that recognises 18 base pairs of the utrophin promoter and efficiently drives utrophin upregulation.BMC molecular biology · 2013Article
- Translating Sleeping Beauty transposition into cellular therapies: victories and challenges.BioEssays : news and reviews in molecular, cellular and developmental biology · 2010Review
- Targeting artificial transcription factors to the utrophin A promoter: effects on dystrophic pathology and muscle function.The Journal of biological chemistry · 2008Article
- Targeted gene insertion for molecular medicine.Journal of molecular medicine (Berlin, Germany) · 2008Review
- Drug-inducible and simultaneous regulation of endogenous genes by single-chain nuclear receptor-based zinc-finger transcription factor gene switches.Gene therapy · 2008Article
- Article
- Suppression of vascular endothelial growth factor expression at the transcriptional and post-transcriptional levels.Nucleic acids research · 2005Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.