Caltech scientists have developed a new method that ferries small-interfering RNA (siRNA) strands into tumors using specialty nanoparticles. Once inside, the siRNA, which was specifically grown to inhibit the expression of the RRM2 gene involved in the tumor cells’ reproduction , is released and is free to do its magic. Because siRNA is used to inhibit the production of a protein necessary for the tumor’s growth, the technique overcomes the difficult task of trying to attack the protein itself.
From a Caltech press release:
Using a new technique developed at Caltech, the team was able to detect and image nanoparticles inside cells biopsied from the tumors of several of the trial’s participants. In addition, Davis and his colleagues were able to show that the higher the nanoparticle dose administered to the patient, the higher the number of particles found inside the tumor cells—the 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."
Caltech podcast of Mark Davis, a leading author of the Nature paper, discussing his RNAi research:
Press release: Caltech-led Team Provides Proof in Humans of RNA Interference Using Targeted Nanoparticles…
Abstract in Nature: Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
(hat tip: Gizmodo)
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