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

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 attached to transferrin, a p rotein that typically carries iron molecules through the bloodstream until it meets up with a transferrin receptor on the surface of another cell. The transferrin binds tightly to a receptor on the cell's surface, where it is drawn inside and surrounded by a small vesicle. The vessels are acidified, causing the nanoparticles to release its contents ?the siRNA.

"Since transferrin receptors are upregulated in tumor cells, this delivery system will home in on tumor cells, leaving normal cells in tact," Hu said.

To test their new delivery system, the scientists targeted tumor cells from the patients of Ewing's sarcoma, a rare and often deadly bone cancer that generally strikes young adults. Despite aggressive therapy, about 40 percent of patients with Ewing's family tumors and 95 percent with metastases die as a result of their disease.

Scientists now recognize that Ewing's sarcoma results when two chromosomes break and trade their genetic content in what's technically called a "translocation," activating the oncogene EWS-FLI1 which triggers the tumor growth characteristic for this cancer.

In their experiment, siRNA was delivered to this growth-promoting region of the tumor cell, effectively reducing cell replication by 80 percent.

The scientists then tried their novel technology in laboratory mice grafted with human Ewing's sarcoma tumors. Following three consecutive days of treatment, the scientists observed strong, but transient, inhibition of tumor growth.

However, when used over longer durations (twice-weekly injections up to four weeks), the results were striking.

"Long-term treatments with this delivery system markedly inhibited tumor growth, with little or no tumor growth in many animals," said Hu.

Future experiments will combine the novel delivery system with small molecular anti-tumor agents, with hopes of creating a new and effective way to treat Ewing's sarcoma and other tumors in the clinic.

"Clinically, Ewing's patients are treated with combination of chemotherapeutic agents, but despite aggressive treatments, the patient outcomes are poor," said Hu.

"The delivery system we're developing can shield the drugs from degradation before reaching the target sites, while delivering siRNA for more specificity and potency so as to lower the required dose for efficacy."

The study was a collaborative effort between the laboratory of Timothy J. Triche, at Children's Hospital of Los Angeles; and the laboratory of Mark E. Davis, at the Caltech. Also participating in the study were Jeremy D. Heidel and Derek W. Barlett, both at Caltech.

Support for this research came from the Las Madrinas endowment in Molecular Genetics and Molecular Pathology at the Children's Hospital of Los Angeles, the Whitaker Foundation, with the National Science Foundation funding part of the work at Caltech.


'"/>

Source:American Association for Cancer Research


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Novel technology detects human DNA mutations
3. Novel antiviral technology inhibits RSV infection in mice
4. Novel Enzyme Shows Potential As An Anti-HIV Target
5. Novel Therapy Tested in Mice Could Chase Away Cat Allergies
6. Discovery Could Lead To Novel Approaches In HIV Treatment
7. Novel ultrafast laser detection of cancer cells also may improve understanding of stem cells
8. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
9. Novel live reporting system to track cells
10. Field of beams - Novel system uses polarized light pulses to reveal crop health
11. Novel compounds show promise as safer, more potent insecticides
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/8/2017)... Feb. 7, 2017 Report Highlights ... 2021 from $8.3 billion in 2016 at a compound ... 2021. Report Includes - An overview of the ... trends, with data from 2015 and 2016, and projections ... Segmentation of the market on the basis of product ...
(Date:2/6/2017)... , Feb. 6, 2017 According ... security are driving border authorities to continue to ... reports there are 2143 Automated Border Control (ABC) ... currently deployed at more than 163 ports of ... 2013 to 2016 achieving a combined CAGR of ...
(Date:2/2/2017)... , Feb. 2, 2017  EyeLock LLC, a market ... new white paper " What You Should Know About ... of ensuring user authenticity is a growing concern. In ... of users. However, traditional authentication schemes such as username/password ... Biometric authentication offers an elegant solution to the ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... , Feb. 24, 2017  OncoSec Medical Incorporated ("OncoSec") ... will host a Key Opinion Leader event to highlight ... oral and poster presentation at the upcoming 2017 ASCO-SITC ... KOL event will be held in-person and via live ... / 9:00 AM PST at the Lotte New York ...
(Date:2/23/2017)... Calif. , Feb. 23, 2017  MIODx ... license for two key immunotherapy technologies from the ... technology provides a method to monitor a patient ... as PD-L1 and CTLA-4.  The second license extends ... a patient is likely to have an immune-related ...
(Date:2/23/2017)... (PRWEB) , ... February 23, ... ... Inc., announced today that in a published evaluation of multiple immunoassay-based threat ... U.S. Department of Energy Laboratory, PathSensors’ CANARY® biosensor threat detection technology was ...
(Date:2/23/2017)... 23, 2017 Aviva Systems Biology Corporation ... acquisition of GenWay Biotech Incorporated, a protein solutions ... product offering for both the research and diagnostic ... and enhance capabilities for both entities. GenWay,s 18 years ... will nicely complement ASB,s objective to become a ...
Breaking Biology Technology: