August 17, 2006

RNA interference advance: getting into the right cells to stop cancer

RNA interference (RNAi) can shutdown bad genes. The problem has been getting them to the right cells. Researchers at Duke University have now designed a simple way to make these therapeutic RNAs and have used them to successfully combat a form of prostate cancer in mice --without adverse effects in other parts of the body. Using the technique, therapeutic RNAs could be designed for many other kinds of cancer and other diseases, according to Bruce Sullenger, chief of experimental surgery at Duke University Medical Center. Sullenger's approach could make it possible to administer RNA therapy through the bloodstream.

The Duke researchers' innovation was to design a region on the RNA itself that directs the therapy to the malignant cells. This directing region is called an aptamer, a section of RNA selected from a large pool of candidates for its ability to bind strongly to a particular molecule -- in this case, a protein that appears on the surface of some prostate cancer cells. The advantage of using such aptamers to direct RNA therapies, says Sullenger, is that manufacturing strands of RNA alone is simpler and less costly than manufacturing strands of RNA attached to something else. RNA also penetrates tissues very well.

After the Duke RNA binds its target on the surface of prostate cancer cells, it is eventually dragged inside the cell. Once inside, the RNA is cleaved in two by a protein native to the cell, freeing the gene-silencing region to find and guide the destruction of its target. RNA interference leads to the destruction of the intermediary between DNA and proteins, called messenger RNA. The Duke therapy destroys the messenger for a gene whose protein prevents prostate cancer cells from dying, even when outside signals tell the cells to do so. With this protection removed, cancer cells died.

Sullenger says that in principle it is possible to use the all-RNA technique to design therapies for many different diseases and infections. Hundreds of tumor markers, for example, are known. Sullenger's lab is engaged in the trial-and-error process of finding RNA sequences that bind protein markers and has found many.

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