Faster drug screening
CAMBRIDGE, Mass. (November 17, 2004) — 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.”
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