May 18, 2009
New RNA Interference Technique Against Cancer

Our genome is coded as DNA. But it gets translated into RNA which serves a variety of roles including as regulatory molecules. Naturally occurring silencing RNAs (siRNAs) are short RNA genetic sequences that bind to other RNAs to suppress genes. Cancer researchers are looking at using siRNAs to try to regulate cancer cells to tell them to stop growing and even to commit cell suicide (apoptosis). Some UCSD researchers are making progress on an siRNA anti-cancer drug delivery mechanism.

In technology that promises to one day allow drug delivery to be tailored to an individual patient and a particular cancer tumor, researchers at the University of California, San Diego School of Medicine, have developed an efficient system for delivering siRNA into primary cells. The work will be published in the May 17 in the advance on-line edition of Nature Biotechnology.

"RNAi has an unbelievable potential to manage cancer and treat it," said Steven Dowdy, PhD, Howard Hughes Medical Institute Investigator and professor of cellular and molecular medicine at UC San Diego School of Medicine. "While there's still a long way to go, we have successfully developed a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells."

RNA interference amounts to attacking cancers at the level of cellular regulation with the siRNAs almost like software patches. Since regulatory mechanisms gone awry cause cancer in the first place the siRNA approach attacks cancer on the level where things go wrong and cells become cancerous. The siRNAs are smaller than DNA delivered as gene therapy. But they are still quite powerful.

Cancers mutate at a fast rate and therefore develop resistance to anti-cancer drugs. The cells in a tumor are not all genetically identical. So natural selection operates on cancer cells in the presence of chemotherapy drugs. Some survive and develop mutations that reduce their vulnerability to chemo and other anti-cancer therapies. But this RNAi approach can be very rapidly adjusted to deal with cancer mutations.

These RNAi methods can be continually tweaked to combat new mutations a way to overcome a major problem associated with current cancer therapies. "Such therapies can't be used a second time if a cancer tumor returns, because the tumor has mutated the target gene to avoid the drug binding," said Dowdy. "But since the synthetic siRNA is designed to bind to a single mutation and only that mutation on the genome, it can be easily and rapidly changed while maintaining the delivery system the PTD-DRBD fusion protein."

We need fast and cheap DNA sequencing and testing to allow rapid retargeting of siRNAs against cancer. This approach turns the war against cancer into an information war. At that level we can win.

Share |      Randall Parker, 2009 May 18 10:52 PM  Biotech Cancer

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