Faster drug screening

CAMBRIDGE, Mass. — Finding molecules that can potentially be developed into therapies is a time-consuming, cumbersome process requiring lots of automated machinery and thousands of ultra small test tubes, or wells, per experiment. Now, scientists at Whitehead Institute for Biomedical Research and Columbia University have developed a way to simplify the process so that a library of 5,000 molecular drug candidates can potentially be screened on a single slide.

At the heart of this new process is a cell-based microarray developed jointly by Whitehead Associate Member David Sabatini and Columbia Assistant Professor Brent Stockwell (a former Whitehead Fellow). In this format, Sabatini and Stockwell print material onto glass slides, then cover the slides with cells. This allows them to test many different reagents quickly, in a miniaturized format. This technology is a modification to an earlier microarray system for studying gene function, developed by Sabatini's lab.

Recently, research assistant Steven Bailey, who was a joint member of the Sabatini lab and Stockwell lab, gave this technique a new twist. Publishing in the November 8 online edition of the journal Proceedings of the National Academy of Sciences, Bailey, Sabatini, and Stockwell used this platform to test a library of small molecules, or drug candidates. Bailey took a series of glass slides and printed the same 72 drug candidates onto each slide. Each molecule was held in place inside of a biodegradable polymer material designed to release of a variety of compounds in a controlled manner. Bailey then covered all the slides with cells, and as the polymer dissolved and released the molecules into the cellular environment, he could test how drug candidates interacted with each of the cells. Also, the slides contained cells in which a different cancer-related gene had been deleted, allowing Bailey to measure possible effects these candidates might have on cancer.

According to Bailey, this platform has a number of advantages over existing techniques. In addition to being able to screen thousands of molecules quickly, a researcher wouldn't need to collect the large number of cells required for traditional approaches in which a separate well is used for each molecule. “In those cases, if you are testing cell types that are rare or slow to divide, it would be difficult to propagate them enough to get all the cells necessary for large-scale screen,” says Bailey. “Here you can screen an entire library of drug targets against those cells on one slide.”