Self-destructing cancer cells? That's what American scientists hope to achieve by developing a new-fangled gene therapy.
Researchers at the University of Rochester have designed a gene that produces a thousand times more protein in cancer cells than in healthy 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.
The researchers said that although trials will be necessary to determine if the difference is enough to destroy tumors without harming healthy tissue, the initial findings are promising.
Vera Gorbunova, assistant professor of biology at the University of Rochester, and her team were investigating Rad51, a protein that is expressed at about five times higher level in cancer cells than in healthy cells.
"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. 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," said Gorbunova.
Gorbunova said that further tests revealed 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.
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.
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.
The researchers 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. Gorbunova said that the results look very promising.
"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," said Gorbunova.
The study is published in early edition of Proceedings of the National Academy of Sciences.