"Using a computerized search of DNA, we were able to identify several hundred potential binding sites for these transcription factors," Corbo explains.

Through a variety of experiments, Corbo's group confirmed that 19 of the new sites are involved in regulation of photoreceptor genes linked to inherited forms of blindness. By studying new and previously established sites, they derived some basic rules or "grammar" that seem to govern how the sites work.

"We've by no means finished defining this grammarit's going to be a major task," he explains. "But what we know now has allowed us to create entirely synthetic cis-regulatory elements which function in photoreceptors. A more complete grammar may even one day allow us to design customized versions of cis-regulatory elements to incorporate into gene therapy vectors for individual patients."

In addition to further studies of the grammar of regulatory sites active in photoreceptor cells, Corbo and others are currently using the results of the study to design gene therapy vectors for a form of Leber's congenital amaurosis, an inherited disorder that leaves patients blind from birth.

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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
25-Jul-2007