February 15, 2009
Researchers Work On RNA Drug To Activate In Cancer Cells

Picture a drug based on RNA as a mini computer program aimed at running in our cells rather than in a silicon computer. Such a drug in theory could carry out much more complex behaviors than conventional simpler chemical compounds. Stanford researchers are working on RNA-based drugs that would only turn on in cancer cells.

Current treatments for diseases like cancer typically destroy nasty malignant cells, while also hammering the healthy ones. Using new advances in synthetic biology, researchers are designing molecules intelligent enough to recognize diseased cells, leaving the healthy cells alone.

"We basically design molecules that actually go into the cell and do an analysis of the cellular state before delivering the therapeutic punch," said Christina Smolke, assistant professor of bioengineering who joined Stanford University in January.

This is the sort of approach we need to wipe out cancer. The current chemo drugs are nowhere near specific enough in the cells they target. The whole body ends up getting damaged. Also, the rates of failure for chemo are very high for many types of cancer.

The trick is to activate only in the presence of biomarker materials that are characteristic of cancer cells. That's a tough job because human cancer cells are human cells. Coming up with suitable biomarkers and ways to make RNA react to them is not easy.

"When you look at a diseased cell (e.g. a cancer cell) and compare it to a normal cell, you can identify biomarkers—changes in the abundance of proteins or other biomolecule levels—in the diseased cell," Smolke said. Her research team has designed molecules that trigger cell death only in the presence of such markers. "A lot of the trick with developing effective therapeutics is the ability to target and localize the therapeutic effect, while minimizing nonspecific side effects," she said.

Smolke will present the latest applications of her lab's work at the American Association for the Advancement of Science (AAAS) meeting in Chicago on Friday, Feb. 13.

These designer molecules are created through RNA-based technologies that Smolke's lab developed at the California Institute of Technology. A recent example of these systems, developed with postdoctoral researcher Maung Nyan Win (who joined Smolke in her move to Stanford), was described in a paper published in the Oct. 17, 2008, issue of Science.

"We do our design on the computer and pick out sequences that are predicted to behave the way we like," Smolke said. When researchers generate these sequences inside the operating system of a cell, they reprogram the cell and change its function. "Building these molecules out of RNA gives us a very programmable and therefore powerful design substrate," she said.

The ability to selectively kill all cancer cells in the body would not only put an end to cancer as a killer but also open up the door to a lot more therapies for other diseases. Hormone replacement therapies that increase the risk of cancer would no longer pose that problem for their use. So we could jack up our aging metabolisms with hormones and pay less of a price for doing so.

Using a sort of hacking approach to drug activation to only turn toxic drugs on in cancer cells is an obvious idea and other groups are working on it. See my 2004 post DNA Nanomachine Computers Against Cancer.

Share |      Randall Parker, 2009 February 15 10:44 PM  Biotech Cancer

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