Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mayo Clinic researchers teach RNA to act as decoy inside living cell to prevent disease activation

19.03.2003


Discovery points to one possible path to novel drug development for cancer, AIDS, some inflammation



Using a new approach, Mayo Clinic researchers have successfully "taught" an RNA molecule inside a living cell to work as a decoy to divert the actions of the protein NF-kappaB, which scientists believe promotes disease development. The findings are published in the current issue of Proceedings of the National Academy of Sciences.

Although it also plays helpful roles in the body, NF-kappaB (pronounced "en-ef-kappa-bee):

  • activates genes that promote cancer-cell survival

  • enables the HIV virus to reproduce, contributing to the onset of AIDS

  • promotes the inflammation process involved in many chronic diseases, such as rheumatoid arthritis

The good news is that once it is diverted by the RNA decoys, NF-kappaB should no longer be available to play its negative role in the chain of molecular events that leads to disease. Mayo’s experimental findings suggest that this could be a new and effective strategy for developing drugs capable of halting the disease process.

In the paper, L. James Maher, III, Ph.D., and Laura Cassiday, Ph.D., Mayo Clinic Department of Biochemistry and Molecular Biology, describe their success with yeast cells and decoy RNA. Under natural conditions in the body, RNA delivers DNA’s plans to cells, which make all the worker proteins to carry out DNA’s executive orders. Drs. Maher and Cassiday have used the RNA/NF-kappaB pairs to divert the NF-kappaB protein. This diversion ensures that the disease-directing capability of NF-kappaB never reaches the DNA.

"We’re trying to develop a somewhat nontraditional drug that is made out of RNA -- which is similar to DNA -- because it has some advantages over other drugs," says Dr. Maher, a molecular biologist. The experiment was performed in his laboratory. "One advantage is that it can be produced by the body’s own cells using a gene-therapy approach in which cells are given the gene for this decoy RNA. But this is a long way off. What’s exciting for us at this point are two discoveries: One is that the small RNAs that we are studying can be taught to do new and exciting things inside living cells. The other is that we have found a new way to use yeast cells as a powerful test system for helping us find the RNAs that are most likely to work in mammalian cells."

"Theoretically, if we want to stop any of these diseases in which NF-kappaB is known to be involved -- cancers, AIDS, some inflammatory diseases -- we’d like to stop the action of this protein; that would be a long-term goal," adds Dr. Cassiday, who is a post-doctoral fellow at Mayo Graduate School. "Our short-term goal is to learn the capabilities of these small, folded RNAs."

The Experiment: How It Works, Where It Leads

Step 1: Test tube experiments

In Dr. Maher’s lab, researchers used a novel approach to finding the right decoy RNAs. Lori Lebruska, Ph.D., a graduate of Mayo Graduate School, took a random collection of one hundred thousand billion (that’s one followed by 14 zeroes) small RNAs. She then mixed the RNAs with NF-kappaB protein and captured the "smartest" RNAs on a filter. After many repeated capture cycles, the RNAs that stuck best to NF-kappaB were the most likely to be competent decoys.

Step 2: Testing the RNA decoy in a living cell.

Drs. Maher and Cassiday had to see if the decoy RNA could bind NF-kappaB not just in a test tube but in the chaos of a cell.

"It’s a whole different ball game in the cell, because there are thousands of other proteins that the RNA might bind to," says Dr. Cassiday. "These proteins could distract it from what we want it to do: find and bind to NF-kappaB. We weren’t sure the RNA was specific enough to target NF-kappaB under these conditions. Also, there are all sorts of enzymes that degrade RNA within a cell. We weren’t sure the RNA would be stable enough to survive and do its job. These were all considerations that needed to be resolved in our cellular experiments."

To test the RNA decoy’s ability to adapt to life inside cells, the researchers chose yeast, which is very similar to human cells, as a model organism.

"The rules change inside the cell," says Dr. Maher. "The real question becomes how can we send the RNA molecules back to school to adapt to these new cellular rules when all they previously knew how to do was succeed with test-tube rules?"

After simultaneously screening thousands of RNA variations in yeast, Drs. Cassiday and Maher found one RNA that had learned to do it all. Dr. Maher notes that by increasing the amount of this molecule, bigger and bigger decoy effects emerge, allowing for significant inhibition of NF-kappaB’s disease capabilities.

The next step for the Mayo research team is to adapt this RNA decoy to life in mammalian cells to see if it can "learn" the additional rules necessary to survive and foil NF-kappaB in its natural setting. If it does, it might one day be a candidate for a new kind of drug therapy.


Shelly Plutowski
507-284-5005 (days)
507-284-2511(evenings)
email: newsbureau@mayo.edu

Shelly Plutowski | EurekAlert!
Further information:
http://www.mayo.edu/
http://www.pnas.org

More articles from Life Sciences:

nachricht Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>