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COMMENTS Staff scientist Pollock Roy of Ariad Gene Therapeutics who specializes in eukaryotic transcriptional regulation, comments that the seq. sepecificity of the transcription factors in the present study is very impressive. He believes that the present study is the first to demonstrate both inhibition & activation of endogenous genes by designed transcription factors, rather than inhibition alone
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TECHNOLOGY Design of Proteins that bind DNA in a highly specific manner & act like TRANSCRIPTION FACTORS to turn endogenous genes on & off in living cells.
"This is the first time, it was possible to show that these designed transcription factors work on real genes & real chromosomes, not genes or binding sites that have been introduced into cells". "It is really possible to knock out expression in a controlled way or elevate the level of expression from the native level to far beyond it to study the role of proteins within the cell". The ability of the designed transcription factors to bind 18-base-pair sequences makes it possible for each of them to target a unique site within the human genome.
The herein developed synthetic transcription factors; are designed proteins contg DNA-binding elements called Zn fingers, structures found in some natural transcription factors.
Natural transcription factors often have both a DNA-binding domain that localizes the protein to a specific site & > one effector domain that activate or repress transcription at or near that site. In the herein designed transcription factors, synthetic Zn finger DNA-binding domains. which are designed to target specific sequences, are combined with natural derived effector domains
UPDATE 02.00
USES The technology can be used to regulate genes of pharma. interest, attack cancer or genetic diseases, control crops, & even "to make flowers bloom when you want them to". The technology also has great potential as a basic research tool. "One could make switches that turn on & turn off genes in a very high-throughput fashion & study the phenotypes of the cells that result".
The author & coworkers show that these designed Zn finger proteins can repress or activate expression of the endoge
nous genes "erbB-2 & erbB-3" in living mouse, monkey & human cells. "ErbB-2" is frequently overexpressed in human breast & ovarian cancer, & expression of "erbB-3" also is suspected to be associated with cancer. In erbB-2 & erbB-3, the 18-base-pair sites targeted by the synthetic proteins share 15 base pairs of common seq, yet enough to regulate one & not the other. The researchers also demonstrate that their transcription factors, & hence gene expression, can be regulated with the drug tetracycline
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