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Modified gene targets cancer cells a thousand times more often than healthy cells
Date:12/17/2008

d in DNA repair, which explains why it's more often expressed in cancer cells. Cancer cells reproduce at accelerated rates, often "not stopping to fix their DNA when they should," says Gorbunova. In these cancer cells, Rad51 is working overtime to repair all the damage, so it's not surprising that it is expressed more often.

Gorbunova believes that when she stripped out part of the Rad51-coding gene, she also stripped out some regulatory elements, which control the production of the protein. Without these elements, healthy cells ignore the gene and do not make the protein. However, these changes have opposite the effect on cancer cells, causing elevated, uncontrolled protein production.

Gobunova and her team have already fused a variant of diphtheria toxin into the Rad51 gene as a "toxic bomb" and tested it on a variety of cancer cell types, including breast cancer, fibrosarcoma, and cervical cancer cells. The results look very promising, she says.

"The early results show the new Rad51 killed all of the cancer cells with minimal if any effect on normal cells," says Gorbunova. "We're very excited. The results are much more striking than anything we would have guessed."

Gorbunova is now working with Stephen Dewhurst, professor of miocrobiology and immunology at the University of Rochester School of Medicine and Dentistry, to design a way to incorporate the new gene with its toxic cargo into a benign virus. If successful, the team will attempt to treat cancer in mice by injecting their tumors with a solution of the virus, and allow the virus to implant the gene into all cells. The key question is whether a dose high enough to kill the cancer cells also will be high enough to kill healthy cells in a living animal, despite the thousand-fold difference in the two cell types' levels of expression.

If the tests are successful, Gorbunova hopes the process might be someday given as a simple shot-in-the-arm, which might travel throughout the bloodstream an
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Contact: Jonathan Sherwood
jonathan.sherwood@rochester.edu
585-273-4726
University of Rochester
Source:Eurekalert

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