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CARY, N.C.—Trana Discovery, a drug discovery company based here, has developed what it says it the "first RNA-RNA high-throughput drug screening assay platform for HIV antivirals" in a collaboration with Birmingham, Ala.-based Southern Research Institute (SRI), a research organization that conducts basic and applied preclinical drug research.
This new HIV high-throughput screening (HTS) assay is designed to give pharmaceutical companies the ability to rapidly and efficiently screen vast libraries of compounds to identify those that interrupt the lifecycle of HIV through a novel mechanism of action—specifically, the inhibition of human transfer RNA (tRNA). Trana says this technology has the potential to discover new classes of medicines for the treatment of HIV that may overcome resistance mechanisms associated with current therapies.
As important as this is, the implications are even more wide-ranging, as the two organizations are also are currently developing other high-throughput screening assays to identity compounds that interrupt the lifecycle of bacteria, such as E. coli and methicillin-resistant Staphylococcus aureus.
"As a not-for-profit research institute, we are always looking for collaborators with interesting or novel biology and chemistry in cancer, infectious disease and neurology in particular," notes David Harris, director of business development, Drug Discovery Division at SRI. "Trana had this interesting new assay system they were developing, and their first target of interest was HIV, so that was most developed of their assay systems and the reason for rolling this one out first."
To the best of SRI and Trana's knowledge, there are no drugs in development right now that deal with this target, so both organizations are excited to be breaking new ground for themselves as well as opening up a new screening tool for other companies to use, Harris notes. "We consider the HIV HTS assay as a major breakthrough in the development of new techniques in the early-stage drug discovery and development process," he adds.
The effort exemplifies one of SRI's major thrusts, which is to take small benchtop-based assays and turn them into high-throughput tools, says E. Lucile White, manager, High-Throughput Screening (HTS) Center and Enzymology for SRI. "When we were initiating discussions with them, they already had an in-house one-person, lab-based assay and they did some initial screening of some of our compounds," she explains. "But it was clear there were limitations of this very good tool being just the benchtop level because it wasn't going to be efficient for large libraries of compounds doing it one compound at a time. So we started talking with them about ways to convert the assay into something suitable for working with automated liquid handling machines."
The initial work to convert the assay took only a couple weeks, though there was also extensive testing and tweaking to make sure results could be replicated. All told, it meant about a month of work spread out over two or three months, White says.
"In recent years, we've really been working hard to go to academia and small companies and turn assays used in their labs into replicatable, robust, high-throughput assays that can be used by other academic institutions and companies. You don't want to run 50,000 or 100,000 or a million samples and find out that something was wrong with the assay parameters and then have to repeat those experiments."
SRI has already had some promising results using the Trana assay on its own extensive compound library, but Harris says he cannot discuss any of the potential candidates or their disease targets at present.
For Trana's part, the company is seeking diverse collections of compounds or compounds with known bioactivity against HIV but unknown mechanisms of action to identify candidates for drug development.
"The development of the HTS assay validates that our technology can be adapted to the automated platforms used for high-throughput screening, and signals a major step forward in its advancement," says Steve Peterson, CEO of Trana Discovery. "We are now ready for the commercialization and licensing of this technology to discover new classes of compounds that will inhibit HIV via a unique mechanism of action."