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 Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>