Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists invent advanced approach to identify new drug candidates from genome sequence

10.02.2014
As proof-of-principle, the team designs potent anti-cancer compound

In research that could ultimately lead to many new medicines, scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed a potentially general approach to design drugs from genome sequence. As a proof of principle, they identified a highly potent compound that causes cancer cells to attack themselves and die.


The new method identified a highly potent compound that causes cancer cells to attack themselves and die.

Credit: Image courtesy of the Disney lab, The Scripps Research Institute.

"This is the first time therapeutic small molecules have been rationally designed from only an RNA sequence—something many doubted could be done," said Matthew Disney, PhD, an associate professor at TSRI who led the study. "In this case, we have shown that that approach allows for specific and unprecedented targeting of an RNA that causes cancer."

The technique, described in the journal Nature Chemical Biology online ahead of print on February 9, 2014, was dubbed Inforna.

"With our program, we can identify compounds with high specificity," said Sai Pradeep Velagapudi, the first author of the study and a graduate student working in the Disney lab. "In the future, we hope we can design drug candidates for other cancers or for any pathological RNA."

In Search of New Approaches

In their research program, Disney and his team has been developing approaches to understand the binding of drugs to RNA folds. In particular, the lab is interested in manipulating microRNAs.

Discovered only in the 1990s, microRNAs are short molecules that work within virtually all animal and plant cells. Typically each one functions as a "dimmer switch" for one or more genes; it binds to the transcripts of those genes and effectively keeps them from being translated into proteins. In this way microRNAs can regulate a wide variety of cellular processes.

Some microRNAs have been associated with diseases. MiR-96 microRNA, for example, is thought to promote cancer by discouraging a process called apoptosis or programmed cell death that can rid the body of cells that begin to grow out of control.

As part of its long-term program, the Disney lab developed computational approaches that can mine information against such genome sequences and all cellular RNAs with the goal of identifying drugs that target such disease-associated RNAs while leaving others unaffected.

"In recent years we've seen an explosion of information about the many roles of RNA in biology and medicine," said Peter Preusch, PhD, of the National Institute of Health's National Institute of General Medical Sciences, which partially funded the research. "This new work is another example of how Dr. Disney is pioneering the use of small molecules to manipulate disease-causing RNAs, which have been underexplored as potential drug targets."

'Unprecedented' Findings

In the new study, Disney and colleagues describe their computational technique, which identifies optimal drug targets by mining a database of drug-RNA sequence ("motif") interactions against thousands of cellular RNA sequences.

Using Inforna, the team identified compounds that can target microRNA-96, as well as additional compounds that target nearly two dozen other disease-associated microRNAs.

The researchers showed that the drug candidate that inhibited microRNA-96 inhibited cancer cell growth. Importantly, they also showed that cells without functioning microRNA-96 were unaffected by the drug.

"This illustrates an unparalleled selectivity for the compound," Disney noted. "In contrast, typical cancer therapeutics target cells indiscriminately, often leading to side effects that can make these drugs difficult for patients to tolerate."

Disney added that the new drug candidate, which is easy to produce and cell permeable, targets microRNA-96 far more specifically than the state-of-the-art method to target RNA (using oligonucleotides) currently in use. "That's unprecedented and provides great excitement for future developments."

In addition to Disney and Velagapudi, Steven M. Gallo of the University of Buffalo was an author of the study, "Sequence-Based Design of Bioactive Small Molecules That Target Precursor MicroRNAs."

The work was supported by the National Institutes of Health (grant R01GM097455) and the Camille and Henry Dreyfus Foundation.

Eric Sauter | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht How molecules teeter in a laser field
18.01.2019 | Forschungsverbund Berlin

nachricht Discovery of enhanced bone growth could lead to new treatments for osteoporosis
18.01.2019 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Additive manufacturing reflects fundamental metallurgical principles to create materials

18.01.2019 | Materials Sciences

How molecules teeter in a laser field

18.01.2019 | Life Sciences

The cytoskeleton of neurons has been found to be involved in Alzheimer's disease

18.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>