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230 B-17 bombers took off from England on the afternoon
of Aug. 17, 1943, to bomb two ball bearing factories in Schweinfurt,
Germany. It was a bold, dangerous mission with incredible promise:
take out the bearings and everything with a wheel -- from vehicles
to machine tools -- no longer functions.
That same principle today is being applied at the cellular level
to treat disease, and a Memphis company intends to be at the center
of it.
Memphis-based Genome Explorations, Inc., has forged a partnership
with ExpressOn Biosystems, of Edinbourgh, Scotland. Genome Explorations
helps scientists identify the genes that are active in their tissue
samples while ExpressOn has a new technology for picking out the
ones that are important.
Genome Explorations has the bombers while ExpressOn has the targeting.
Eldon Geisert, a professor of ophthalmology at the University of
Tennessee Health Science Center, likes to remember that many historians
still consider the raids on Schweinfurt as a brilliant idea that
didn't work.
"This is still a developing technology; the main thing it's
good for is blocking the expression of specific genes," Geisert
says. "We've had technology in the past with similar promise
that failed."
He is among several local scientists who intend to experiment with
ExpressOn's Accessarray 4000 technology.
The technology had its beginnings in Holland where flower breeders
were experimenting with artificial genes and attempting to create
a daffodil with a much deeper purple. Instead, the flowers turned
out white. The breeders managed to block a critical gene involved
in color, stopping that entire process.
What they had done was interfere with what's known as messenger
RNA by binding to it. Messenger RNA carries the blueprint for a
particular protein, in this case the protein leads to colored flowers.
In other cases, the particular protein produces cancer and thousands
of other things good and bad.
"This is a major discovery in science, the small-interference
RNA," says Dan Goldowitz. "It's a normal product of a
cell to dampen down expressions and correct mistakes. Now researchers
are starting to jump on this and thinking about making these things
synthetically, and selectively suppressing genes."
Goldowitz is a professor of anatomy and neurobiology and director
of the UT Research Center of Excellence in Genomics and Bioinformatics.
He's both hopeful and cautious as he prepares tissue samples for
the first round.
"20 years ago the magic bullet was using antibodies to inhibit
pathways, but that has not borne out for lots of reasons,"
he says. "A lot of the current hoopla is in that realm. It's
non-toxic and very selective. The potential is that if you can knock
out a particular gene and prevent a cascade from happening, then
this disease doesn't happen."
The idea is much more elegant compared to drugs, which are fairly
indiscriminate. But interfering with the messengers is not 100%
effective.
"If you're still eking out 20%, is that enough to make you
sick?" Goldowitz says.
One use Geisert is interested in involves the abnormal proliferation
of cells in the retina of diabetics. He's still designing his interference
agents and hopes to create one that will shut down the process.
Genome Explorations provides gene profiling to researchers, essentially
telling them which genes in a sample are switched on and active.
This helps scientists understand which genes are working as a team,
and to know which ones to pursue. The company uses technology from
Affymetrix, Inc., of Santa Clara, Calif., to sort through 400,000
genes and identify a few hundred which are active.
Plenty of genes are switched on but just hanging around. The next
question is knowing which of the genes are actively involved in
producing a disease. The only way to do this is to knock out each
gene, and see what happens.
"Right now that's done with a mouse, and it takes over a year
for your results," says Divyen Patel, CEO of Genome Explorations.
"With ExpressOn we can knock out the gene in a cell and see
what the cell does. It allows us to look at the effect of any knockout
gene in just three days."
Aside from the time involved, running a knockout sequence in mice
can cost $100,000. ExpressOn's services start at $500.
"Messenger RNA is like a ball of string; you need to know which
areas are available for binding," says Darrin Disley, head
of marketing at ExpressOn. "The current technology has you
snip one base at a time, but a gene can have 10,000 bases so you
have to do so many experiments. There's a very high failure rate;
it's expensive and slow."
ExpressOn provides results in a few hours with very precise targets.
The company has completed three rounds of venture capital funding.
"Everyone has a gene of interest," Disley says. "People
today are looking at around 60,000-70,000 genes, and every one of
them is a potential customer."
Genome Explorations is already an exclusive service provider to
ExpressOn, and Patel expects to close a deal soon that would make
his company the exclusive distributor in North America.
Contact staff writer Scott Shepard at 259-1724
or sshepard@bizjournals.com
Copyright 2004 American City Business Journals Inc.
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