Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Enhancing RNA Interference

Published: Wednesday, June 26, 2013
Last Updated: Wednesday, June 26, 2013
Bookmark and Share
Helping RNA escape from cells’ recycling process could make it easier to shut off disease-causing genes.

Nanoparticles that deliver short strands of RNA offer a way to treat cancer and other diseases by shutting off malfunctioning genes. Although this approach has shown some promise, scientists are still not sure exactly what happens to the nanoparticles once they get inside their target cells.

A new study from MIT sheds light on the nanoparticles’ fate and suggests new ways to maximize delivery of the RNA strands they are carrying, known as short interfering RNA (siRNA).

“We’ve been able to develop nanoparticles that can deliver payloads into cells, but we didn’t really understand how they do it,” says Daniel Anderson, the Samuel Goldblith Associate Professor of Chemical Engineering at MIT. “Once you know how it works, there’s potential that you can tinker with the system and make it work better.”

Anderson, a member of MIT’s Koch Institute for Integrative Cancer Research and MIT’s Institute for Medical Engineering and Science, is the leader of a research team that set out to examine how the nanoparticles and their drug payloads are processed at a cellular and subcellular level. Their findings appear in the June 23 issue of Nature Biotechnology. Robert Langer, the David H. Koch Institute Professor at MIT, is also an author of the paper.

One RNA-delivery approach that has shown particular promise is packaging the strands with a lipidlike material; similar particles are now in clinical development for liver cancer and other diseases.

Through a process called RNA interference, siRNA targets messenger RNA (mRNA), which carries genetic instructions from a cell’s DNA to the rest of the cell. When siRNA binds to mRNA, the message carried by that mRNA is destroyed. Exploiting that process could allow scientists to turn off genes that allow cancer cells to grow unchecked.

Scientists already knew that siRNA-carrying nanoparticles enter cells through a process, called endocytosis, by which cells engulf large molecules. The MIT team found that once the nanoparticles enter cells they become trapped in bubbles known as endocytic vesicles. This prevents most of the siRNA from reaching its target mRNA, which is located in the cell’s cytosol (the main body of the cell).

This happens even with the most effective siRNA delivery materials, suggesting that there is a lot of room to improve the delivery rate, Anderson says.

“We believe that these particles can be made more efficient. They’re already very efficient, to the point where micrograms of drug per kilogram of animal can work, but these types of studies give us clues as to how to improve performance,” Anderson says.

Molecular traffic jam

The researchers found that once cells absorb the lipid-RNA nanoparticles, they are broken down within about an hour and excreted from the cells.

They also identified a protein called Niemann Pick type C1 (NPC1) as one of the major factors in the nanoparticle-recycling process. Without this protein, the particles could not be excreted from the cells, giving the siRNA more time to reach its targets. “In the absence of the NPC1, there’s a traffic jam, and siRNA gets more time to escape from that traffic jam because there is a backlog,” says Gaurav Sahay, an MIT postdoc and lead author of the Nature Biotechnology paper.

In studies of cells grown in the lab without NPC1, the researchers found that the level of gene silencing achieved with RNA interference was 10 to 15 times greater than that in normal cells.

Lack of NPC1 also causes a rare lysosomal storage disorder that is usually fatal in childhood. The findings suggest that patients with this disorder might benefit greatly from potential RNA interference therapy delivered by this type of nanoparticle, the researchers say. They are now planning to study the effects of knocking out the NPC1 gene on siRNA delivery in animals, with an eye toward testing possible siRNA treatments for the disorder.

The researchers are also looking for other factors involved in nanoparticle recycling that could make good targets for possibly slowing down or blocking the recycling process, which they believe could help make RNA interference drugs much more potent. Possible ways to do that could include giving a drug that interferes with nanoparticle recycling, or creating nanoparticle materials that can more effectively evade the recycling process.

“This paper describes a new and very important way to improve the potency of siRNA delivery systems by inhibiting proteins that recycle imported material back out of the cell,” says Pieter Cullis, a professor of biochemistry and molecular biology at the University of British Columbia who was not part of the research team. “It is possible that this approach will give rise to the order-of-magnitude improvements in potency required for siRNA-based therapeutics to be more generally effective agents to treat disease.”


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 3,300+ scientific posters on ePosters
  • More than 4,900+ 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

Protecting Privacy in Genomic Databases
System helps ensure databases used in medical research will not leak patients’ personal information.
Wednesday, August 10, 2016
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Wednesday, July 27, 2016
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Friday, July 08, 2016
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Friday, May 27, 2016
A Programming Language for Living Cells
New language lets researchers design novel biological circuits.
Monday, April 04, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
A New Way to Discover DNA Modifications
Researchers systematically find molecules that help regulate and protect DNA.
Wednesday, March 02, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
How Cancer Cells Spread
Study offers new targets for drugs that may prevent cancer from spreading.
Thursday, December 17, 2015
Scaling Up Synthetic-Biology Innovation
MIT professor’s startup makes synthesizing genes many times more cost effective.
Monday, December 14, 2015
Delivering microRNAs for Cancer Treatment
Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
Wednesday, December 09, 2015
CRISPR-Cas9 Genome Editing Hurdle Overcome
Team re-engineers system to dramatically cut down on editing errors; improvements advance future human applications.
Thursday, December 03, 2015
Scientific News
Breast Cancer Cells Found To Switch Molecular Characteristics
Spontaneous interconversion between HER2-positive and HER2-negative states could contribute to progression, treatment resistance in breast cancer.
Some Breast Cancer Patients With Low Genetic Risk Could Skip Chemotherapy
Genetic test can help predict survival and guide treatment options.
Lose Weight, Escape the Eight: Weight-Based Cancer Risk
IARC has identified eight additional cancer sites linked to overweight and obesity.
Coffee Consumption Linked to Genes
Researchers have identified a gene that influences coffee consumption. The gene is thought to relate to caffeine breakdown.
Emerging Model of Cancer
Cancer acts cooperatively, making individual decisions but acting in unison; this insight is being used to create a computer model of cancer.
Biological Barcodes Using CRISPR
Using genome editing tools, researchers are getting closer to understand differentiation of various cell types during development.
Controlling DNA Repair
Scientists discover that DNA repair outcomes following CRISPR-Cas9 cleaving are non-random and can be harnessed to produce desired effects.
Demonstrating LNP Delivery of CRISPR Components
Intellia has presented data demonstrating in vivo gene editing ising liquid nanoparticles (LNPs) to deliver CRISPR/Cas9.
Gene Therapy Via Ultrasound
Research into a gene therapy approach called sonoporation could help combat heart disease and cancer.
Creating Embryos with 'Heteroplasmy'
New discovery in genetic research could lead to treatments for mitochondrial diseases.
Skyscraper Banner

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!