Download Development of recombinant DNA technolgy

Before it was known how to manipulate living organisms, many materials that
are used to benefit human health and industry were first isolated from natural resources.
One example is the drug urokinase, which is used to break up blood clots following
myocardial infarction. Twenty years ago, urokinase was purified from urine that was
collected from public rest areas along highways.
However, the development of
recombinant DNA technology has made it possible to produce urokinase in large
amounts at low cost by introducing the gene into microorganisms and growing them to
produce the drug. In addition to urokinase, more than one hundred useful materials are
now produced using recombinant DNA technology. Generally, microorganisms, such as
E. coli and yeast, and animal cells, such as Chinese hamster ovary cells, are used to
produce these materials in large amounts. For example, the vaccine used to prevent
hepatitis B virus infection was first produced by collecting defective virus particles
from the blood of hepatitis B virus carriers. However, this vaccine could potentially be
contaminated with viral DNA, which can cause a hepatoma, or other infectious
materials. Now, the vaccine is produced using recombinant yeast that has been modified
to produce the antigen by introducing the virus antigen gene. Korea used to have to
purchase the blood of hepatitis B virus carriers from China to produce vaccine, but
using recombinant DNA technology we can now produce surplus hepatitis B vaccine
and export it to other countries.
Although microorganisms and animal cells are still the most popular hosts, these
systems have possible pitfalls. For example, material produced using microorganisms
might differ slightly from that produced in animal cells, making it less effective than the
naturally available product, and perhaps causing unwanted immune responses in
humans.
For example, because the human growth hormone produced from
microorganisms is slightly different from that of humans, an injection of human growth
hormone from microorganisms sometimes induces an immune response against the
hormone, rendering it ineffective. In addition, material produced using animal cells can
contain contaminants, such as unwanted infectious materials, since serum from cows is
added to animal cell cultures. Therefore, extreme caution must be taken to eliminate all
possible contaminants from such products during the purification procedure, and this
process increases production costs significantly.
Until the early 1990s, plants were not considered useful for producing
recombinant material owing to several technological shortfalls. For example, plants and
plant cells grow too slowly in comparison with microorganisms and animal cells, and
there was also no efficient vector system for delivering desirable genes into plant cells.
With the recent accumulation of knowledge on plant molecular biology and the
development of an efficient vector system that uses bacteria which infect plants and
produce plant tumors, researchers are starting to consider plants for producing useful
materials. Plant cells can be grown in very inexpensive media and require only sugars
and salts for their growth, making plant-based expression systems very cost effective,
with much lower production costs than other expression systems. In addition, plants do
not require potentially harmful materials for their growth, such as the bovine serum that
is essential for growing animal cells.
Over the last seven years, our team has been concentrating on establishing a
plant expression system for producing useful materials. Initially, we examined the
production of cytokines, which are very expensive compounds that modulate biological
responses in human and animals.
One cytokine, granulocyte macrophage-colony
stimulating factor (GM-CSF), is used to increase the number of blood cells in patients
who have undergone bone marrow
transplantation to treat leukemia,
and we are successfully producing
this and other valuable cytokines.
We are very excited to have
developed a way to produce human
interleukin-12, a potent anti-tumor agent that cannot be produced from microorganisms.
Based on our results with human interleukin-12, we have also succeeded in producing
other therapeutic and diagnostic antibodies that also cannot be produced from
microorganisms. Consequently, our laboratory has been designated a National Research
Laboratory by the Ministry of Science and Technology in 2000, and is also supported by
the Next Generation Technology Program of the Ministry of Commerce, Industry, and
Energy.
We are also studying the use of plants as an expression system to produce
antigens to develop edible vaccines. Put simply, we want to produce transgenic plants
that contain antigens in their tissue and that act as vaccines when eaten. We believe that
this technology will prove very useful for producing vaccines against animal diseases
and for vaccinating children. This method has several advantages, as it avoids the high
cost of vaccinating animals by injection and it spares children the pain of conventional
vaccine injections. In addition, many countries have neither sufficient refrigerated
facilities to store conventional vaccines nor enough health care workers to administer
them. In such countries, edible vaccines should prove a very useful delivery system.
This technology was first suggested in 1990, and researchers now believe that
commercial edible vaccines might be available within the next 3 to 5 years. We started
research in this area in 1997.
Our
primary
targets
for
developing plant-based edible
vaccines are animal diseases,
since
clinical
testing
and
application is much easier than
when working with humans,
although we are also targeting human diseases such as Dengue virus infection. These
projects are currently supported by several grants, including a 21st Century Frontier
Project from the Ministry of Science and Technology.
The technologies that we are researching and developing might not prove
commercially viable for a few years. Moreover, several points must be resolved before
these technologies can be used successfully for practical purposes. However, research
in new areas is always very interesting and challenging. Drs. Yong-Suk Jang and DaeHyuk Kim of the Division of Biological Sciences are collaborating in the research
projects
described
above
in
the
genetics/biotechnology, respectively.
fields
of
immunology
and
molecular
In addition, several researchers from other
institutes and countries, such as the United States, Japan, Vietnam, Hungary, and
France, are collaborating with us in this research.