Featured Research

from universities, journals, and other organizations

Breakthrough approach to quickly identify new drug candidates from genome sequence

Date:
February 9, 2014
Source:
Scripps Research Institute
Summary:
In research that could ultimately lead to many new medicines, scientists from the Florida campus of The Scripps Research Institute have developed a potentially general approach to design drugs from genome sequence.

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

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.

"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.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sai Pradeep Velagapudi; Steven M. Gallo; and Matthew Disney. Sequence-Based Design of Bioactive Small Molecules That Target Precursor MicroRNAs. Nature Chemical Biology, February 9, 2014 (in press)

Cite This Page:

Scripps Research Institute. "Breakthrough approach to quickly identify new drug candidates from genome sequence." ScienceDaily. ScienceDaily, 9 February 2014. <www.sciencedaily.com/releases/2014/02/140209152346.htm>.
Scripps Research Institute. (2014, February 9). Breakthrough approach to quickly identify new drug candidates from genome sequence. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2014/02/140209152346.htm
Scripps Research Institute. "Breakthrough approach to quickly identify new drug candidates from genome sequence." ScienceDaily. www.sciencedaily.com/releases/2014/02/140209152346.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins