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Caltech-led Team Provides Proof in Humans of RNA Interference Using Targeted Nanoparticles

Researchers unveil scientific results from siRNA Phase I clinical trial in cancer patients

A California Institute of Technology (Caltech)-led team of researchers and clinicians has published the first proof that a targeted nanoparticle—used as an experimental therapeutic and injected directly into a patient’s bloodstream—can traffic into tumors, deliver double-stranded small interfering RNAs (siRNAs), and turn off an important cancer gene using a mechanism known as RNA interference (RNAi).  Moreover, the team provided the first demonstration that this new type of therapy, infused into the bloodstream, can make its way to human tumors in a dose-dependent fashion—i.e., a higher number of nanoparticles sent into the body leads to a higher number of nanoparticles in the tumor cells.

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, the team was 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.

Mark Davis, PhD, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, is the research team’s leader.  The Phase I trial—sponsored by Calando Pharmaceuticals—is proceeding at START and UCLA's Jonsson Comprehensive Cancer Center, and the clinical results of the trial will be presented at a later time.

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