As proof-of-principle, the team designs a 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.
“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.”
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.”
The Latest on: New medicines
via Google News
The Latest on: New medicines
- In Other Views: New drug to treat ALSon September 18, 2022 at 12:10 pm
Few diseases are as cruelly debilitating as amyotrophic lateral sclerosis (ALS). But a Food and Drug Administration advisory committee last week gave patients a glimmer of hope by backing a ...
- This team of doctors reveals how to avoid a massive pitfall in making new drugson September 18, 2022 at 12:00 pm
Identifying and addressing the barriers to enrolling in research that patients face can increase participation and lead to better patient care.
- New uses for old drugs? Every Cure offers hope for people with rare diseaseson September 18, 2022 at 7:27 am
The new nonprofit Every Cure, backed by the Clinton Global Initiative, aims to identify generic drugs that could help people with rare diseases.
- New Garda recruits could face drug tests as force aims to stamp out corruptionon September 18, 2022 at 1:07 am
New rules on drug testing for gardai will come into effect before the year is out, the Department of Justice pledged this week. It is one of 34 recommendations in a garda inspectorate report on ...
- How O.J. Howard is defining a new era of Achilles recoveries in sports medicineon September 17, 2022 at 12:30 pm
O.J. Howard’s one-inch scar blistered near the center of his right heel, and its miniscule existence atop a once-torn Achilles tendon may very well represent the difference in the Texans tight end’s ...
- Marijuana Retail Licenses in New York Are Going First to Those Convicted of Drug Crimeson September 17, 2022 at 6:24 am
The state’s $200 million equity program is targeted at the “justice involved” in a controversial effort to redress the impacts of the war on drugs.
- New medicine to protect babies and infants from respiratory syncytial virus (RSV) infectionon September 17, 2022 at 1:46 am
EMA has recommended a marketing authorisation in the European Union for Beyfortus (nirsevimab) for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in newborn babies ...
- OUTSIDE VIEW: New drug offers rare hope for patients if approved by FDAon September 16, 2022 at 10:00 pm
Few diseases are as cruelly debilitating as amyotrophic lateral sclerosis (ALS). But a Food and Drug Administration advisory committee this week gave patients a glimmer of hope by backing a ...
- Briefcase: UNM school of medicine hires new physicianon September 16, 2022 at 5:26 pm
Dr. Ariana Barkley has been hired by the Pediatric Neurosurgery Division at the University of New Mexico’s School of Medicine. Barkley, who was born in Port of Spain and raised in Ontario, attended ...
- Experts Say New Street Drug Is 'as Deadly as Fentanyl'on September 16, 2022 at 1:46 pm
Nitazenes -- powerful illicit synthetic opioids -- are increasingly being added into heroin and street versions of opioid pills and triggering fatal overdoses, ...
via Bing News