Nanotechnology Now

Our NanoNews Digest Sponsors



Heifer International

Wikipedia Affiliate Button


android tablet pc

Home > Press > RNA Interference Delivered Using Nanoparticles Hits Target in Human Patients

Abstract:
A multi-institutional team of researchers and clinicians has published the first proof that a targeted nanoparticle can traffic into tumors, deliver double-stranded small interfering RNAs (siRNAs), and turn off the production of an important cancer protein 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, that is, a higher number of nanoparticles sent into the body leads to a higher number of nanoparticles in the tumor cells.

RNA Interference Delivered Using Nanoparticles Hits Target in Human Patients

Bethesda, MD | Posted on April 20th, 2010

These two findings were achieved in phase I clinical trials in which the investigators are testing a nanoparticle-siRNA construct as an anticancer therapy.

These results, which were published in 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 team leader Mark E. Davis of the California Institute of Technology. Dr. Davis is also a member of the Nanosystems Biology Cancer Center, a National Cancer Institute Center for Cancer Nanotechnology Excellence.

The discovery of RNAi, 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 such as cancer has been highly touted.

"RNAi is a new way to stop the production of proteins," says Dr. Davis. What makes it such a potentially powerful tool, he adds, is the fact that its target is not a protein, the typical target for anticancer drugs. 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 Dr. 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. Dr. Davis, however, had a solution. Even before the discovery of RNAi, he and his team had begun working on ways to deliver nucleic acids to cells via the blood stream. They eventually created a four-component system, featuring a unique polymer called cyclodextrin, that self-assembles in the presence of RNA into a targeted, siRNA-containing nanoparticle. The siRNA delivery system is under clinical development by Calando Pharmaceuticals, Inc., based in Pasadena, California.

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

As part of their study, the team was able to detect and image nanoparticles inside cells biopsied from the tumors of several of the phase I trial's participants. In addition, Dr. 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, Dr. 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 - the target of the siRNA encapsulated in the nanoparticle - 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 Dr. 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."

This work, which is detailed in a paper titled, "Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. Investigators from the Jonsson Compresensive Cancer Center, the University of California, Los Angeles, South Texas Accelerated Research Therapeutics (START), the City of Hope Comprehensive Cancer Center, and Calando Pharmaceuticals also participated in this study. An abstract of this paper is available at the journal's Web site.

####

About NCI Alliance for Nanotechnology in Cancer
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.

The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.

Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.

For more information, please click here

Copyright © NCI Alliance for Nanotechnology in Cancer

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Creation of 'Rocker' protein opens way for new smart molecules in medicine, other fields December 18th, 2014

How does enzymatic pretreatment affect the nanostructure and reaction space of lignocellulosic biomass? December 18th, 2014

Silicon Valley-Based Foresight Valuation Launches STR-IP™, a New Initiative for Startups to Discover the Value of Their Intellectual Property December 18th, 2014

Iranian Scientists Use Nanotechnology to Increase Power, Energy of Supercapacitors December 18th, 2014

Govt.-Legislation/Regulation/Funding/Policy

Zenosense, Inc. - Hospital Collaboration - 400 Person Lung Cancer Detection Trial December 17th, 2014

SUNY Poly NanoCollege Faculty Member Selected as American Physical Society Fellow: SUNY Poly Associate Professor of Nanoscience Dr. Vincent LaBella Recognized for Significant Technological Innovations that Enable Interactive Learning December 17th, 2014

Switching to spintronics: Berkeley Lab reports on electric field switching of ferromagnetism at room temp December 17th, 2014

ORNL microscopy pencils patterns in polymers at the nanoscale December 17th, 2014

Possible Futures

A novel method for identifying the body’s ‘noisiest’ networks November 19th, 2014

Researchers discern the shapes of high-order Brownian motions November 17th, 2014

VDMA Electronics Production Equipment: Growth track for 2014 and 2015 confirmed: Business climate survey shows robust industry sector November 14th, 2014

Open Materials Development Will Be Key for HP's Success in 3D Printing: HP can make a big splash in 3D printing, but it needs to shore up technology claims and avoid the temptation of the razor/razor blade business model in order to flourish November 11th, 2014

Academic/Education

SUNY Poly NanoCollege Faculty Member Selected as American Physical Society Fellow: SUNY Poly Associate Professor of Nanoscience Dr. Vincent LaBella Recognized for Significant Technological Innovations that Enable Interactive Learning December 17th, 2014

Nanomedicine expert joins Rice faculty: Gang Bao combines genetic, nano and imaging techniques to fight disease December 17th, 2014

FEI and Oregon Health & Science University Install a Complete Correlative Microscopy Workflow in Newly Built Collaborative Science Facility December 16th, 2014

Student Nanotechnology Laboratories Network Set Up in Iran December 15th, 2014

Nanomedicine

Creation of 'Rocker' protein opens way for new smart molecules in medicine, other fields December 18th, 2014

Iranian Researchers Produce Electrical Pieces Usable in Human Body December 18th, 2014

Unraveling the light of fireflies December 17th, 2014

First Home-Made Edible Herbal Nanodrug Presented to Pharmacies across Iran December 17th, 2014

Announcements

Creation of 'Rocker' protein opens way for new smart molecules in medicine, other fields December 18th, 2014

How does enzymatic pretreatment affect the nanostructure and reaction space of lignocellulosic biomass? December 18th, 2014

Silicon Valley-Based Foresight Valuation Launches STR-IP™, a New Initiative for Startups to Discover the Value of Their Intellectual Property December 18th, 2014

Iranian Scientists Use Nanotechnology to Increase Power, Energy of Supercapacitors December 18th, 2014

Nanobiotechnology

Scientists trace nanoparticles from plants to caterpillars: Rice University study examines how nanoparticles behave in food chain December 16th, 2014

FEI and Oregon Health & Science University Install a Complete Correlative Microscopy Workflow in Newly Built Collaborative Science Facility December 16th, 2014

UCLA engineers first to detect and measure individual DNA molecules using smartphone microscope December 15th, 2014

Biomimetic dew harvesters: Understanding how a desert beetle harvests water from dew could improve drinking water collection in dew condensers December 8th, 2014

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







© Copyright 1999-2014 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE