Big numbers

Trana and SRI team up to turn benchtop assay into high-throughput tool for HIV and more

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CARY, N.C.—Trana Discovery, a drug discovery company basedhere, has developed what it says it the "first RNA-RNA high-throughput drug screeningassay platform for HIV antivirals" in a collaboration with Birmingham,Ala.-based Southern Research Institute (SRI), a research organization thatconducts basic and applied preclinical drug research.

This new HIV high-throughput screening (HTS) assay isdesigned to give pharmaceutical companies the ability to rapidly andefficiently screen vast libraries of compounds to identify those that interruptthe lifecycle of HIV through a novel mechanism of action—specifically, theinhibition of human transfer RNA (tRNA). Trana says this technology has thepotential to discover new classes of medicines for the treatment of HIV thatmay 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 otherhigh-throughput screening assays to identity compounds that interrupt thelifecycle of bacteria, such as E. coli and methicillin-resistant Staphylococcusaureus.

"As a not-for-profit research institute, we are alwayslooking for collaborators with interesting or novel biology and chemistry incancer, infectious disease and neurology in particular," notes David Harris,director of business development, Drug Discovery Division at SRI. "Trana hadthis interesting new assay system they were developing, and their first targetof interest was HIV, so that was most developed of their assay systems and thereason for rolling this one out first."

To the best of SRI and Trana's knowledge, there are no drugsin development right now that deal with this target, so both organizations areexcited to be breaking new ground for themselves as well as opening up a newscreening tool for other companies to use, Harris notes. "We consider the HIVHTS assay as a major breakthrough in the development of new techniques in theearly-stage drug discovery and development process," he adds.

The effort exemplifies one of SRI's major thrusts, which isto take small benchtop-based assays and turn them into high-throughput tools,says E. Lucile White, manager, High-Throughput Screening (HTS) Center andEnzymology for SRI. "When we were initiating discussions with them, theyalready had an in-house one-person, lab-based assay and they did some initialscreening of some of our compounds," she explains. "But it was clear there werelimitations of this very good tool being just the benchtop level because itwasn't going to be efficient for large libraries of compounds doing it onecompound at a time. So we started talking with them about ways to convert theassay into something suitable for working with automated liquid handlingmachines."

The initial work to convert the assay took only a coupleweeks, though there was also extensive testing and tweaking to make sure resultscould be replicated. All told, it meant about a month of work spread out overtwo or three months, White says.

"In recent years, we've really been working hard to go toacademia and small companies and turn assays used in their labs intoreplicatable, robust, high-throughput assays that can be used by other academicinstitutions and companies. You don't want to run 50,000 or 100,000 or amillion samples and find out that something was wrong with the assay parametersand then have to repeat those experiments."

SRI has already had some promising results using the Tranaassay on its own extensive compound library, but Harris says he cannot discussany of the potential candidates or their disease targets at present.

For Trana's part, the company is seeking diverse collectionsof compounds or compounds with known bioactivity against HIV but unknownmechanisms of action to identify candidates for drug development.

"The development of the HTS assay validates that ourtechnology can be adapted to the automated platforms used for high-throughputscreening, and signals a major step forward in its advancement," says StevePeterson, CEO of Trana Discovery. "We are now ready for the commercializationand licensing of this technology to discover new classes of compounds that willinhibit HIV via a unique mechanism of action."

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