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Novel gene-silencing nanoparticles shown to inhibit Ewing's sarcoma

Anaheim, Calif. -- A novel delivery system that transports gene silencing nanoparticles into tumor cells has been shown to inhibit Ewing's sarcoma in an animal model of the disease.

In this classic "Trojan horse" approach, a protein called transferrin that normally delivers iron into cells is modified to also smuggle into tumor cells siRNA (short interfering RNA) encased in nano-sized sugar polymers. The siRNA was designed to target a specific growth-promoting gene called EWS-FLI1 that's active only in Ewing's sarcoma tumors.

Once inside these cells, the genetic machinery of the tumor cells are effectively silenced or shut down, preventing further growth.

"This is the first study to show that systemic administration of siRNA can inhibit disseminated tumor growth," said Siwen Hu, a postdoctoral fellow at Children's Hospital of Los Angeles and the University of Southern California, and one of the study's lead investigators.

"We conclude that this novel delivery system is a powerful and simple method to induce gene silencing, with the potential to move to clinical trials," said Hu, who presented the results at the 96th Annual Meeting here of the American Association for Cancer Research.

In recent years, scientists have been intrigued by the potential of siRNA to block the activity of genes that promote the growth of tumors. Harnessing the power of this new technology, however, has proved daunting for a variety of reasons, including the ability to deliver these bits of genetic material in high concentrations to specific tumor sites, while avoiding degradation.

To overcome these hurdles, the scientists employed a sugar-containing polymer invented by chemical engineers at the California Institute of Technology. For this experiment, the polymer binds to and condenses the engineered siRNA into nanoparticles that, in effect, form a protective shield around their precious genetic cargo. These nanoparticles, in turn, are attache
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Contact: Warren R. Froelich
froelich@aacr.org
215-440-9300
American Association for Cancer Research
19-Apr-2005


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