Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors
説明
Epigenetic control of transcription is essential for mammalian development and its deregulation causes human disease. For example, loss of proper imprinting control at the IGF2-H19 domain is a hallmark of cancer and Beckwith-Wiedemann syndrome, with no targeted therapeutic approaches available. To address this deficiency, we engineered zinc-finger transcription proteins (ZFPs) that specifically activate or repress the IGF2 and H19 genes in a domain-dependent manner. Importantly, we used these ZFPs successfully to reactivate the transcriptionally silent IGF2 and H19 alleles, thus overriding the natural mechanism of imprinting and validating an entirely novel avenue for 'transcription therapy' of human disease.
収録刊行物
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- Gene Therapy
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Gene Therapy 10 513-522, 2003-03-01
Springer Science and Business Media LLC
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キーワード
- Male
- Beckwith-Wiedemann Syndrome
- Reverse Transcriptase Polymerase Chain Reaction
- Zinc Fingers
- Genetic Therapy
- Wilms Tumor
- Kidney Neoplasms
- Genomic Imprinting
- Gene Expression Regulation
- Insulin-Like Growth Factor II
- Neoplasms
- Gene Targeting
- Humans
- Female
- Genes, Tumor Suppressor
- Genetic Engineering
- Transcription Factors