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Arkansas Biosciences Institute,
Worcester Polytechnic Institute, issue joint news release on
interleukin-12 production in genetically modified tobacco plants
WORCESTER, Mass. and JONESBORO, Ark.
--
Dec. 3, 2008 --
Interleukin-12
is a naturally occurring protein essential for the proper functioning of
the human immune system. Having either too much or too little
interleukin-12 may play a role in the development of many diseases,
including some cancers and auto-immune disorders like Crohn’s,
psoriasis, and rheumatoid arthritis. In turn, modulating interleukin-12
levels could yield new therapies for those conditions.
In an
effort to
create
a new and cost-effective method for producing interleukin-12 and make
more of the scarce protein available for research and therapeutic
development, a team of scientists at Worcester Polytechnic Institute’s
Life Sciences and Bioengineering Center (WPI) and the Arkansas
Bioscience Institute at Arkansas State University (ABI) reports that
hairy roots from genetically modified tobacco plants can be grown in a
contained novel mist bioreactor system, yielding significant quantities
of murine interleukin-12. A paper detailing the results of the study has
been published early, online, by the journal Biotechnology and
Bioengineering and will appear in the journal’s printed edition
early in 2009.
“We are very encouraged by the results of this study,” says Pamela J.
Weathers, PhD, professor of biology and biotechnology at WPI, and
co-author of the paper. “Interluekin-12 is a valuable protein and there
just isn’t enough available for biomedical research, let alone for
therapeutic development. Our study shows that we can use plants to
produce interleukin-12, and other therapeutic proteins, in a
cost-effective controlled process.”
The tobacco project is one of several emerging collaborative efforts
between WPI and ABI. In the current study, tobacco plants were modified
in the lab of Carole Cramer, PhD, ABI’s executive director and co-author
of the paper. Cramer’s team successfully inserted into tobacco plants a
mouse gene that directs the production of interleukin 12. Hairy root
cultures from those modified tobacco plants were then grown in a mist
reactor developed in the Weathers lab. As its name implies, the mist
reactor uses ultrasonic technology to spray a fine mist of water and
nutrients on the root cultures, which are suspended in a plastic bag.
The nutrient solution is collected at the bottom of the bag and recycled
through the system. In this way, all of the materials are completely
contained and isolated from the environment. “Some have concerns about
growing genetically modified plants in an open field where they could
cross-pollinate with other species. Our mist reactor overcomes those
concerns because the system is completely contained,” Weathers says.
“There is no interaction with the environment, and once we’ve collected
the therapeutic proteins grown in the roots, all the remaining material
is safely destroyed.”
Traditional pharmaceuticals, like aspirin or statins for lowering
cholesterol, are made by synthesizing and combining chemicals in a
factory-like production setting. Therapeutic proteins are biologic
molecules produced in living cells, which are then isolated, purified
and prepared for use in treating disease. For example, insulin is a
therapeutic protein now produced by inserting a human insulin gene into
bacteria, which in turn prompts the bacteria to make human insulin.
Using plants as a production system for therapeutic proteins can not
only be more cost-effective than animal cell-based production, but can
also significantly reduce the risk of contamination by animal or human
viruses or pathogens.
In the current study, Weathers compared the capabilities of the mist
reactor with two other common methods for growing plant cultures—the
shake flask method and the airlift bioreactor. The results showed the
mist reactor produced the highest concentration of interleukin 12. “Our
system is simple and scalable. We’ll use these data to optimize this
kind of process and scale it up to the next level,” Weathers said.
On the genetics side, the current study used a mouse gene as a model to
test the idea and the process. Now, with positive results in hand,
Cramer’s team can begin to study a human interleukin-12 gene’s ability
to direct the production of the human protein in tobacco plants. "Making
large complex pharmaceutical proteins in a way that is highly
reproducible, scalable, and not cost prohibitive is quite challenging,”
Cramer says. “The mist reactor seems excellent for producing
high-quality proteins for vaccine trials and therapeutic applications.”
The mist reactor’s capabilities are not restricted to tobacco roots. The
system is being tested on several other plant cultures, including
Artemisia annua, which naturally produces very small quantities of
an effective antimalarial molecule known as artemisinin. “With our
colleagues in Arkansas, we are making good progress on developing the
technology and understanding the biology that will allow us to use
plants to help create new pharmaceuticals and other chemical building
blocks essential for a healthy society and environment,” Professor
Weathers said.
About
Worcester Polytechnic Institute
Founded in 1865 in Worcester, Mass., WPI was one of the nation's first
engineering and technology universities. WPI's14 academic departments
offer more than 50 undergraduate and graduate degree programs in
science, engineering, technology, management, the social sciences, and
the humanities and arts, leading to bachelor’s, master’s and PhD
degrees. WPI's world-class faculty work with students in a number of
cutting-edge research areas, leading to breakthroughs and innovations in
such fields as biotechnology, fuel cells, and information security,
materials processing, and nanotechnology. Students also have the
opportunity to make a difference to communities and organizations around
the world through the university's innovative Global Perspective
Program. There are more than 20 WPI project centers throughout North
America and Central America, Africa, Australia, Asia, and Europe.
About
The Arkansas Biosciences Institute
The
Arkansas Biosciences Institute is a five member research consortium
funded by Arkansas’ Tobacco Settlement Proceeds Act of 2000. The
Consortium is focused on cutting edge research at the interface of
agriculture and medicine with the long term goal of enhancing the health
of Arkansans and the nation. At Arkansas State University, a new
state-of-the-art research building was constructed to house this new
endeavor with a grand opening held in September 2004. Since 2004,
dynamic cross-disciplinary research clusters have been developed in four
target areas: plant-based bioproduction of proteins for medical and
biofuels applications; plant metabolic engineering; molecular
innovations in food sciences; and the interface of environment,
agriculture, and human disease.
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