Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Incurable Brain Cancer Gene Is Silenced

Published: Wednesday, November 06, 2013
Last Updated: Wednesday, November 06, 2013
Bookmark and Share
Gene regulation technology increases survival rates in mice with glioblastoma.

Glioblastoma multiforme (GBM), the brain cancer that killed Sen. Edward Kennedy and kills approximately 13,000 Americans a year, is aggressive and incurable. Now a Northwestern University research team is the first to demonstrate delivery of a drug that turns off a critical gene in this complex cancer, increasing survival rates significantly in animals with the deadly disease.

The novel therapeutic, which is based on nanotechnology, is small and nimble enough to cross the blood-brain barrier and get to where it is needed -- the brain tumor. Designed to target a specific cancer-causing gene in cells, the drug simply flips the switch of the troublesome oncogene to “off,” silencing the gene. This knocks out the proteins that keep cancer cells immortal.

In a study of mice, the nontoxic drug was delivered by intravenous injection. In animals with GBM, the survival rate increased nearly 20 percent, and tumor size was reduced three to four fold, as compared to the control group. The results are published today (Oct. 30) in Science Translational Medicine.

“This is a beautiful marriage of a new technology with the genes of a terrible disease,” said Chad A. Mirkin, a nanomedicine expert and a senior co-author of the study. “Using highly adaptable spherical nucleic acids, we specifically targeted a gene associated with GBM and turned it off in vivo. This proof-of-concept further establishes a broad platform for treating a wide range of diseases, from lung and colon cancers to rheumatoid arthritis and psoriasis.”

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.

Glioblastoma expert Alexander H. Stegh came to Northwestern University in 2009, attracted by the University’s reputation for interdisciplinary research, and within weeks was paired up with Mirkin to tackle the difficult problem of developing better treatments for glioblastoma.

Help is critical for patients with GBM: The median survival rate is 14 to 16 months, and approximately 16,000 new cases are reported in the U.S. every year.

In their research partnership, Mirkin had the perfect tool to tackle the deadly cancer: spherical nucleic acids (SNAs), new globular forms of DNA and RNA, which he had invented at Northwestern in 1996, and which are nontoxic to humans. The nucleic acid sequence is designed to match the target gene.

And Stegh had the gene: In 2007, he and colleagues identified the gene Bcl2Like12 as one that is overexpressed in glioblastoma tumors and related to glioblastoma’s resistance to conventional therapies.

“My research group is working to uncover the secrets of cancer and, more importantly, how to stop it,” said Stegh, a senior co-author of the study. “Glioblastoma is a very challenging cancer, and most chemo-therapeutic drugs fail in the clinic. The beauty of the gene we silenced in this study is that it plays many different roles in therapy resistance. Taking the gene out of the picture should allow conventional therapies to be more effective.”

Stegh is an assistant professor in the Ken and Ruth Davee Department of Neurology at the Northwestern University Feinberg School of Medicine and an investigator in the Northwestern Brain Tumor Institute.

The power of gene regulation technology is that a disease with a genetic basis can be attacked and treated if scientists have the right tools. Thanks to the Human Genome Project and genomics research over the last two decades, there is an enormous number of genetic targets; having the right therapeutic agents and delivery materials has been the challenge.

“The RNA interfering-based SNAs are a completely novel approach in thinking about cancer therapy,” Stegh said. “One of the problems is that we have large lists of genes that are somehow disregulated in glioblastoma, but we have absolutely no way of targeting all of them using standard pharmacological approaches. That’s where we think nanomaterials can play a fundamental role in allowing us to implement the concept of personalized medicine in cancer therapy.”

Stegh and Mirkin’s drug for GBM is specially designed to target the Bcl2Like12 gene in cancer cells. Key is the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells, but these spherical nucleic acids can. Small interfering RNA (siRNA) surrounds a gold nanoparticle like a shell; the nucleic acids are highly oriented, densely packed and form a tiny sphere. (The gold nanoparticle core is only 13 nanometers in diameter.) The RNA’s sequence is programmed to silence the disease-causing gene.

“The problems posed by glioblastoma and many other diseases are simply too big for one research group to handle,” said Mirkin, who also is the director of Northwestern’s International Institute for Nanotechnology. “This work highlights the power of scientists and engineers from different fields coming together to address a difficult medical issue.”

Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the technology now is the basis of powerful commercialized and FDA-cleared medical diagnostic tools. This new development, however, is the first realization that the nanostructures injected into an animal naturally find their target in the brain and can deliver an effective payload of therapeutics.

The next step for the therapeutic will be to test it in clinical trials.

The nanostructures used in this study were developed in Mirkin’s lab on the Evanston campus and then used in cell and animal studies in Stegh’s lab on the Chicago campus.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Gene Shown to Cause Parkinson’s Disease
Northwestern Medicine scientists have discovered a new cause of Parkinson’s disease – mutations in a gene called TMEM230. This appears to be only the third gene definitively linked to confirmed cases of Parkinson’s disease.
Tuesday, June 07, 2016
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Friday, April 29, 2016
Nanoparticle Acts Like Trojan Horse To Halt Asthma
New technology also can be used to turn off peanut and other food allergies
Tuesday, April 19, 2016
Investigating Kidney Cancer Therapies
Two drugs known to improve survival for patients with metastatic renal cell carcinoma do not reduce the risk of cancer recurrence when administered after surgery.
Wednesday, April 13, 2016
New Predictor of Cancer
When your biological age is older than your chronological age, the risk of getting and dying of cancer rises
Friday, February 19, 2016
Where Cancer Cells May Begin
Scientists use fruit fly genetics to understand how things could go wrong in cancer.
Monday, January 25, 2016
Tracking How Herpes Simplex Virus Moves Through Cells
In a recent study, Derek Walsh, PhD, associate professor of Microbiology-Immunology, and his team showed how the herpes simplex virus (HSV) exploits microtubule plus-end tracking proteins to initiate transport and infection in human cells.
Friday, November 13, 2015
Circadian Clock Controls Insulin and Blood Sugar in Pancreas
Map of thousands of genes suggests new therapeutic targets for diabetes.
Tuesday, November 10, 2015
Low Dose Beta-Blockers As Effective As High Dose After a Heart Attack?
Heart attack patients live as long – or even longer – on one-quarter the suggested dose.
Monday, September 28, 2015
Network Control: Letting Noise Lead The Way
Research team leverage cells' noisy nature to keep them healthy.
Monday, September 21, 2015
New Protein Manufacturing Process Unveiled
Scientists now have a way to study special proteins associated with disease.
Monday, September 14, 2015
Protein Found to Control Inflammatory Response
A new Northwestern Medicine study shows that a protein called POP1 prevents severe inflammation and, potentially, diseases caused by excessive inflammatory responses.
Monday, August 24, 2015
Data Mining DNA For Polycystic Ovary Syndrome Genes
A new Northwestern Medicine genome-wide association study of PCOS – the first of its kind to focus on women of European ancestry – has provided important new insights into the underlying biology of the disorder.
Friday, August 21, 2015
Scientists Find What Controls Waking Up and Going to Sleep
Simple two-cycle mechanism turns key brain neurons on or off during 24-hour day.
Monday, August 17, 2015
Uncovering Genetic Factors in Leukemia
Northwestern Medicine scientists have discovered how a gene linked to leukemia functions, a finding that may have important implications for children with Down syndrome who have a higher risk of developing the blood cancer.
Thursday, August 06, 2015
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
How Cancer Spreads in the Body
Cancer cells appear to depend on an unusual survival mechanism to spread around the body, according to an early study led by Queen Mary University of London.
Fix for 3-Billion-Year-Old Genetic Error
Researchers at The University of Texas at Austin have developed a fix that allows RNA to accurately proofread for the first time.
“Amazing Protein Diversity” Discovered in Maize
The genome of the corn plant – or maize, as it’s called almost everywhere except the US – “is a lot more exciting” than scientists have previously believed. So says the lead scientist in a new effort to analyze and annotate the depth of the plant’s genetic resources.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!