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

ation needed to make a protein in the first place.

"In principle," says Davis, "that means every protein now is druggable because its inhibition is accomplished by destroying the mRNA. And we can go after mRNAs in a very designed way given all the genomic data that are and will become available."

Still, there have been numerous potential roadblocks to the application of RNAi technology as therapy in humans. One of the most problematic has been finding a way to ferry the therapeutics, which are made up of fragile siRNAs, into tumor cells after direct injection into the bloodstream. Davis, however, had a solution. Even before the discovery of RNAi, he and his team had begun working on ways to deliver nucleic acids into cells via systemic administration. They eventually created a four-component systemfeaturing a unique polymerthat can self-assemble into a targeted, siRNA-containing nanoparticle. The siRNA delivery system is under clinical development by Calando Pharmaceuticals, Inc., a Pasadena-based nanobiotech company.

"These nanoparticles are able to take the siRNAs to the targeted site within the body," says Davis. Once they reach their targetin this case, the cancer cells within tumorsthe nanoparticles enter the cells and release the siRNAs.

The scientific results described in the Nature paper are from a Phase I clinical trial of these nanoparticles that began treating patients in May 2008. Phase I trials are, by definition, safety trials; the idea is to see if and at what level the drug or other therapy turns harmful or toxic. These trials can also provide an in-human scientific proof of conceptwhich is exactly what is being reported in the Nature paper.

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 nanopart
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Contact: Jon Weiner
jrweiner@caltech.edu
626-395-3226
California Institute of Technology
Source:Eurekalert  

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Caltech-led team provides proof in humans of RNA interference using targeted nanoparticles
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