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

Scripps Florida Scientists Devise New Way to Dramatically Raise RNA Treatment Potency

Published: Thursday, August 08, 2013
Last Updated: Thursday, August 08, 2013
Bookmark and Share
As proof-of-principle, drug candidate powerfully neutralizes myotonic dystrophy defect in cell culture.

Scientists from the Jupiter campus of The Scripps Research Institute (TSRI) have shown a novel way to dramatically raise the potency of drug candidates targeting RNA, resulting in a 2,500-fold improvement in potency and significantly increasing their potential as therapeutic agents.

The new study, published recently online ahead of print by the journal Angewandte Chemie, confirms for the first time that a small molecule actually binds to a disease-causing RNA target—a breakthrough that should help scientists identify precise RNA targets within living cells, profile their interactions, and predict drug candidates’ side effects.

“We’re trying to make tools that can target any RNA motif,” said Matthew Disney, a TSRI associate professor who authored the research with a research associate in his lab, Lirui Guan. “This study completely validates our design—it validates that our compound targets the desired RNA sequence in a complex cellular environment that contains many hundreds of thousands of RNAs.”
While targeting DNA has been used as a therapeutic strategy against cancer, few similar approaches have been attempted for disease-associated RNAs.

In the new study, the scientists created a small molecule that binds to the genetic defect in RNA that causes myotonic dystrophy type 1 and improves associated defects in cell culture.

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. In this case, the repetition of the cytosine-uracil-guanine (CUG) in the RNA sequence leads to disease by binding to a particular protein, MBNL1, rendering it inactive and resulting in a number of protein-splicing abnormalities.

To achieve the increase in the drug candidate’s potency, Disney and his colleagues attached a reactive molecule (a derivative of chlorambucil, a chemotherapy drug that has been used to treatment a form of leukemia) to the small molecule they had identified. As a result, the new compound not only binds to the target, it becomes a permanent part of the target—as if it were super glued to it, Disney said. Once attached, it switches off the CUG defect and prevents the cell from turning it back on.

Disney was surprised at the approximately 2,500-fold improvement in potency with the new approach.

“I was shocked by the increase,” he said. “This takes the potency into the realm where one would like to see if the compound were to have real therapeutic potential.”

As a result, the new compound, known as 2H-4-CA, is the most potent compound known to date that improves DM1-associated splicing defects. Importantly, 2H-4-CA does not affect the alternative splicing of a transcript not regulated by MBNL1, demonstrating selectivity for the CUG repeat and suggesting that it might have minimal side effects.

“We can now use this approach to attach reactive molecules to other RNA targeted small molecules,” Disney said.

The reactive molecule model also provides a potentially general method to identify cellular targets of RNA-directed small molecules. Such probes could also identify unintended targets, information that could be used to design and identify compounds with improved selectivity in an approach similar to activity-based profiling, Disney said.


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

Influencing the Immune System
A TSRI study has opened the door to influencing the immune system, yielding possible boosts to vaccine efficiency and immunology.
Tuesday, August 02, 2016
New Cancer Drug Target Found in Dual-Function Protein
Findings from a study from TSRI have shown that targeting a protein called GlyRS might help to halt cancer growth.
Wednesday, June 29, 2016
Breakthrough Approach to Breast Cancer Treatment
Scripps scientists have designed a drug candidate that decreases growth of breast cancer cells.
Tuesday, May 24, 2016
Scripps Research Institute Scientists Capture Picture of 'MicroRNA' in Action
The Findings Will Help Guide Drug Design.
Thursday, October 30, 2014
Chemists Discover Cancer Drug Candidate Structure
Chemists at The Scripps Research Institute have determined the correct structure of a highly promising anticancer compound approved by the U.S. FDA for clinical trials in cancer patients.
Wednesday, May 21, 2014
Revealing Molecular Secrets Behind the Health Benefits of Wine
Resveratrol has been much in the news as the component of grapes and red wine associated with reducing “bad cholesterol,” heart disease and some types of cancer.
Wednesday, April 30, 2014
Scripps Research Appoints Cancer Biologist
Christoph Rader is appointed as associate professor in the Department of Cancer Biology and the Department of Molecular Therapeutics.
Monday, August 06, 2012
Scripps Research Institute Scientists Find the Structure of a Key ‘Gene Silencer’ Protein
The structure reveals potential therapeutic targets in area with ‘untapped potential’.
Monday, April 30, 2012
Scripps Research Scientists Create Novel RNA Repair Technology
Discovery could aid search for Huntington’s, Spinocerebellar Ataxia, and Kennedy Disease treatments.
Thursday, January 19, 2012
Small RNAs may Play Big Role in Embryonic Stem Cells
A new study led by Scripps researchers could increase understanding of stem cells and advance development of potential therapies.
Saturday, April 12, 2008
Scientific News
Oxygen Can Impair Cancer Immunotherapy in Mice
Researchers at NIH have discovered that the T cells contain a group of oxygen-sensing proteins which act to limit inflammation within the lungs.
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.
Unravelling the Metastatic Mechanism of Melanoma
Research has uncovered the mechanism of melanoma spreading; the findings could lead to a cure for the disease.
Gene Therapy Via Ultrasound
Research into a gene therapy approach called sonoporation could help combat heart disease and cancer.
Novel MRI Technique Distinguishes Healthy Prostate Tissue from Cancer
The UTSW researchers have determined that glucose stimulates release of the zinc ions from inside epithelial cells, which they could then track on MRIs.
Precision Nanobots Target Cancerous Tumours
Researchers achieve breakthrough toward redefining anti-cancer drug administration using nanorobotics.
PARP Proteins Explore Therapeutic Targets in Cancer
Researchers at UTSW have identified a previously unknown role of a certain class of proteins that opens the door to explore therapeutic targets in cancer and other disease.
Novel Therapeutic Approach for Blood Disorders
Gene editing of human blood-forming stem cells mimics a benign genetic condition that helps to overcome sickle cell disease and other blood disorders.
Immune-Cell Population Predicts Immunotherapy Response in Melanoma
All patients with high levels of one immune-cell type responded to treatment.
Effects of Chemotherapy on Developing Ovaries in Female Fetuses
Researchers at University of Edinburgh have shown that etoposide can damage the development of the ovaries while a fetus is in the womb.
SELECTBIO

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!