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):
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. Mayos 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 DNAs plans to cells, which make all the worker proteins to carry out DNAs 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.
"Were 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 bodys 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. Whats 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 -- wed 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. Mahers 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 (thats 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.
"Its 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 werent 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 werent 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 decoys 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-kappaBs 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.
Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)
Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.
In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...
Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
23.09.2016 | Event News
20.09.2016 | Event News
16.09.2016 | Event News
23.09.2016 | Life Sciences
23.09.2016 | Health and Medicine
23.09.2016 | Life Sciences