Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scripps Florida Scientists Create New Approach to Destroy Disease-Associated RNAs in Cells

Published: Friday, December 21, 2012
Last Updated: Friday, December 21, 2012
Bookmark and Share
As proof of principle, team creates molecule that corrects myotonic dystrophy in living cells.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed a new approach to alter the function of RNA in living cells by designing molecules that recognize and disable RNA targets. As a proof of principle, in the new study the team designed a molecule that disabled the RNA causing myotonic dystrophy.

The study, published online ahead of print on December 20, 2012 by the journal Angewandte Chemie, reports the creation of small molecules that recognize disease-associated RNAs, targeting them for destruction. Since small molecules are cell-permeable, the approach could have benefits over traditional methods of targeting RNAs for degradation, such as antisense or RNA interference (RNAi).

“We’re excited about these results,” said Matthew Disney, an associate professor at TSRI who pioneered the research. “This approach may allow for the inactivation of many cellular RNAs by small molecules and potentially lead the way to a whole range of novel therapeutics.”

It’s well known that gene expression can be controlled by triggering the degradation of messenger RNA—the blueprint for the production of proteins. This is accomplished through the recruitment of compounds that cleave or split the molecule. While several compounds can induce RNA cleavage in vitro, this has not been accomplished efficiently in living cells—until now.

In the new study, Disney and Research Associate Lirui Guan attached a rationally designed small molecule that targets the RNA that causes myotonic dystrophy type 1 with a molecule that produces hydroxyl radicals. Upon the small molecule’s recognition of the target, a hydroxyl radical was released that cleaved the disease-associated RNA, alleviating the disease-associated defects. Disney noted that, despite the compound’s producing a highly reactive species, the compounds are non-toxic at relatively effective doses.

The team accomplished this feat through what Disney calls a bottom-up approach to targeting RNA.

“We first identified the preferred RNA structural elements or motifs that bind to small molecules,” he said. “Then we looked at these elements in RNAs that cause disease and designed a binding molecule with increased affinity and specificity for those elements.”

Myotonic dystrophy type 1 involves a type of RNA defect known as a “triplet repeat,” a series of three nucleotides repeated more times than normal in an individual’s genetic code, resulting in a number of protein splicing abnormalities. Symptoms of this variable disease can include wasting of the muscles and other muscle problems, cataracts, heart defects and hormone changes.

The applications for this new approach could include cancer treatment in conjunction with other therapies, Disney said. The approach could also be used to create chemical probes of RNA function or to develop tools to probe RNA structure—provided, of course, that the RNA-binding preferences of the small molecules involved were well defined.


Further Information
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 2,400+ scientific posters on ePosters
  • More than 3,700+ 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

Scripps Scientists Awarded NIH Grant for Biomarker Studies
$2.3 million grant awarded to develop new diagnostics for cancer, rheumatoid arthritis, colitis.
Tuesday, May 06, 2014
Chemists Devise Inexpensive, Benchtop Method for Marking and Selecting Cells
Chemists at The Scripps Research Institute have found an easier way to perform one of the most fundamental tasks in molecular biology.
Wednesday, January 16, 2013
Scientists Find Structure of a Protein that Makes Cancer Cells Resistant to Chemotherapy
A research team at the Scripps Research Institute has obtained the first glimpse of a protein that keeps certain substances, including many drugs, out of cells.
Monday, March 30, 2009
Scientific News
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Oxitec ‘Self-Limiting Gene’ Offers Hope for Controlling Invasive Moth
A new pesticide-free and environmentally-friendly way to control insect pests has moved ahead with the publication of results showing that Oxitec diamondback moths (DBM) with a ‘self-limiting gene’ can dramatically reduce populations of DBM.
Teeth Reveal Lifetime Exposures to Metals, Toxins
Researchers have identified dental biomarkers to reveal links between early iron exposure and late life brain diseases.
Scientists Identify Schizophrenia’s “Rosetta Stone” Gene
Scientists have identified a critical function of what they believe to be schizophrenia’s “Rosetta Stone” gene that could hold the key to decoding the function of all genes involved in the disease.
Could a simple saliva test detect Alzheimer's?
Researchers have presented findings suggesting that a simple, non-invasive diagnostic for Alzheimer's could be within reach.
New Research Advances Genetic Studies in Wildlife Conservation
‘Next-gen’ DNA sequencing of non-invasively collected hair expands field of conservation genetics.
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!