Modified gene targets cancer cells 1,000 times more often

December 18th, 2008 - 1:55 pm ICT by IANS  

Washington, Dec 18 (IANS) Researchers have designed a gene that is a thousand times more effective against cancer cells than healthy cells. The findings may help address the prime challenge in anti-cancer therapy: improving treatments’ ability to specifically and effectively target cancer cells. Using this new approach, scientists should be able to insert “self-destruct” codes into the modified gene, forcing cancer cells to kill themselves while healthy cells remain largely unaffected.

Vera Gorbunova and Andrei Seluanov, both assistant professors of biology at the University of Rochester and graduate student Christopher Hine were investigating Rad51, a protein that is expressed at about five times higher level in cancer cells than in healthy cells, when they stumbled on something very unexpected.

“We stripped off some of the Rad51 gene and replaced it with a marker protein DNA to see why Rad51 was five times more abundant in cancer cells,” says Gorbunova, according to a Rochester university statement. The study was published in the Proceedings of the National Academy of Sciences.

“We wanted to see if there was any way we could boost that difference and create a really useful cancer-targeting tool. We couldn’t believe it when we saw the cancer cells expressing the engineered Rad51 around a thousand times more.”

When Gorbunova first saw the huge discrepancy, she thought one of her graduate students had fumbled the lab test. Further tests showed that the altered Rad51 was expressed in some cancer cells as much as 12,500 times as often as healthy cells.

Such a large discrepancy means scientists should be able to use it to create versions of Rad51 that carry a “toxic bomb”, which only the cancer cells will trigger.

Gorbunova 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. We’re very excited. The results are much more striking than anything we would have guessed.”

Rad51 is normally involved 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”, said 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.

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