Churning Out New Life Forms: Made-To-Order DNA
Pastor Dale Morgan
Churning Out New Life Forms: Made-To-Order DNA*
Apr 10th, 2007 8:12 AM
By Emily Singer
Installing one of those prefab, snap-together wood-flooring kits is a
lot easier than shaping and sanding rough planks. Adapting a similar
construction strategy, a biotech startup called Codon Devices, based in
Cambridge, MA, aims to streamline genetic engineering. It makes
made-to-order DNA strands, freeing scientists from the finicky work it
takes to put together a complicated piece of DNA the old-fashioned way.
That capability could soon change the face of molecular biology. As it
becomes cheaper and cheaper to create large chunks of genetic material
from scratch, scientists will be able to make ever more complex
biological creations. "In the next few years, we'll probably see people
engineering cells to do drug delivery or creating cellular sensors,"
says George Church, a professor of genetics at Harvard and one of
Codon's founders. "Maybe even cells that make inorganic objects of
interest, like nanostructures."
Codon was founded in 2005 just as the fledgling field of synthetic
biology--the quest to design and build new life forms that can perform
useful functions--was beginning to take off. The ability to make complex
genetic constructs is a cornerstone of the field, allowing scientists to
use chunks of DNA to design novel biological parts, which can then be
inserted into bacteria or other cells. (See "Synthetic Biology on Display.")
While DNA synthesis is still too expensive to replace more-traditional
molecular-biology methods on a broad scale, experts say that the
DNA-synthesis market is about to boom, much as the DNA-sequencing market
has in the past few years. As sequencing costs plummeted, the number of
sequencing projects surged, with record numbers of genomes--even entire
microbial communities--being sequenced. "As large companies begin to
adopt this technology, the volumes of DNA synthesis will explode," says
John Danner, president and chief executive officer of Codon. "When that
happens, thousands of scientists will think about this when they go to
sleep at night, and that will change how biotech is done."
Last summer, the company created what it believes was the biggest piece
of man-made DNA, a 35,000 base-pair strand incorporating several genes
needed to synthesize a pharmaceutical compound. The DNA was made for
Microbia, another Cambridge-based biotech, which is creating microbes to
manufacture specialty chemicals. But the potential applications are
broad, spanning pharmaceuticals, energy, and agriculture.
Synthetic biologists are excited about the prospects, but they're still
waiting for a decrease in price to the point that they can afford to do
the experiments they want to do. "Cost is the critical component to
making this technology work," says Chris Voigt, a synthetic biologist at
the University of San Francisco. "Right now, we can design one construct
that costs a fortune to make. But we want to be able to order different
components put together in different ways so we can study the critical
factor in putting them together."
Codon is confident that that day will soon come. It plans to use its
enhanced synthesis capacity to find better enzymes for industrial
processes. Since nature hasn't always come up with the most effective
proteins, scientists often design a more effective enzyme by tweaking
the DNA code used to make it. But it's difficult to predict in advance
which tweaks will produce the best enzymes. Codon is now using its
synthesis technology to carry out that process en masse--it makes
millions of copies of the same genetic construct with slight
variations--and then tests them to figure out which does its job best.
For example, scientists are now hot on the trail of the ideal
cellulase--an enzyme that can break down cellulose in plants.
More-efficient cellulases are important for producing cellulosic
ethanol, which is ethanol derived from waste biomass rather than from
corn starch or sugarcane, and therefore more cost-effective. "We can
take the sequence for the cellulose enzyme in, say, a termite's gut, use
a computer program to figure out different ways to optimize the
sequence, churn out a million different versions, and then test them to
find the top ten forms," says Brian Baynes, chief scientific officer and
cofounder of Codon.
The same process could be used to develop protein-based drugs that can
better bind to their targets or more efficiently break down a toxin in
the blood. "Knowing that they can test variations of things will get
molecular biologists working more like engineers," says Danner.
The company is planning to open an expanded production facility, which
will operate much like any other mass-production facility, except its
product will be DNA. Codon intends to build a facility, slated to open
this summer, that's much larger than current needs warrant to prepare
for the DNA-synthesis boom.
Copyright Technology Review 2007.