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Caltech-led team provides proof in humans of RNA interference using targeted nanoparticles
Date:3/21/2010

icle dose administered to the patient, the higher the number of particles found inside the tumor cellsthe first example of this kind of dose-dependent response using targeted nanoparticles.

Even better, Davis says, the evidence showed the siRNAs had done their job. In the tumor cells analyzed by the researchers, the mRNA encoding the cell-growth protein ribonucleotide reductase had been degraded. This degradation, in turn, led to a loss of the protein.

More to the point, the mRNA fragments found were exactly the length and sequence they should be if they'd been cleaved in the spot targeted by the siRNA, notes Davis. "It's the first time anyone has found an RNA fragment from a patient's cells showing the mRNA was cut at exactly the right base via the RNAi mechanism," he says. "It proves that the RNAi mechanism can happen using siRNA in a human."

"There are many cancer targets that can be efficiently blocked in the laboratory using siRNA, but blocking them in the clinic has been elusive," says Antoni Ribas, associate professor of medicine and surgery at UCLA's Jonsson Comprehensive Cancer Center. "This is because many of these targets are not amenable to be blocked by traditionally designed anti-cancer drugs. This research provides the first evidence that what works in the lab could help patients in the future by the specific delivery of siRNA using targeted nanoparticles. We can start thinking about targeting the untargetable."

"Although these data are very early and more research is needed, this is a promising study of a novel cancer agent, and we are proud of our contribution to the initial clinical development of siRNA for the treatment of cancer," says Anthony Tolcher, director of clinical research at South Texas Accelerated Research Therapeutics (START).

"Promising data from the clinical trials validates our years of research at City of Hope into ribonucleotide reductase as a target for novel gene-based therapies for
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Contact: Jon Weiner
jrweiner@caltech.edu
626-395-3226
California Institute of Technology
Source:Eurekalert  

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