Scientists use nanotech robots as cancer gene therapy for first time in humans
Caltech-led team provides proof in humans of RNA interference using targeted nanoparticles
Mar 21 2010, 2:20 PM EST
Researchers unveil scientific results from siRNA Phase I clinical trial in cancer patients
PASADENA, Calif.A California Institute of Technology (Caltech)-led team of researchers and clinicians has published the first proof that a targeted nanoparticleused as an experimental therapeutic and injected directly into a patient's bloodstreamcan 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 fashioni.e., a higher number of nanoparticles sent into the body leads to a higher number of nanoparticles in the tumor cells.
These results, published in the March 21 advance online edition of the journal Nature, demonstrate the feasibility of using both nanoparticles and RNAi-based therapeutics in patients, and open the door for future "game-changing" therapeutics that attack cancer and other diseases at the genetic level, says Mark Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, and the research team's leader.
Image Caption: This targeted nanoparticle used in the study and shown in this schematic is made of a unique polymer and can make its way to human tumor cells in a dose-dependent fashion. Credit: Caltech/Derek Bartlett Usage Restrictions: With credit as given.
The discovery of RNA interference, the mechanism by which double strands of RNA silence genes, won researchers Andrew Fire and Craig Mello the 2006 Nobel Prize in Physiology or Medicine. The scientists first reported finding this novel mechanism in worms in a 1998 Nature paper. Since then, the potential for this type of gene inhibition to lead to new therapies for diseases like cancer has been highly touted.
"RNAi is a new way to stop the production of proteins," says Davis. What makes it such a potentially powerful tool, he adds, is the fact that its target is not a protein. The vulnerable areas of a protein may be hidden within its three-dimensional folds, making it difficult for many therapeutics to reach them. In contrast, RNA interference targets the messenger RNA (mRNA) that encodes the information 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."
(more at the article linked in the headline)
