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With the high costs of the technology needed to produce Hepatitis B medical
solutions, developing countries aren't obtaining all the help they need.
Inexpensive transgenic plants that produce biopharmaceuticals may help
change that, November 2004 by Mark Finlayson.

Ever since the early 20th century, antibodies from immune serum have
played an important role in treating many infectious diseases, including
Hepatitis B. The treatment involves the administration of antibodies, gained
from either animal or human donors, to a person currently suffering from the
disease. Strict safety standards have to be met when preparing the
antibodies from the donor sera. In addition, manufacturing costs, along with
consumer prices, are accordingly high, often making it a non-option in
particular for developing countries. Thus researchers have turned their
attention elsewhere to look for other large scale treatment possibilities.

Producing the pharmaceutical products in genetically modified plants seems a
promising way of cutting costs, while at the same time offering a wide range
of advantages. One such advantage is that plant cells not only have fewer
human infectious agents than mammalian cells, but are also relatively easy
to grow in culture. A second advantage is plants grown in greenhouses, or in
the field, need very little resources in comparison to conventional
production methods. Plants would not require much more than soil, light,
water and a few agrochemicals to thrive. With plants, production is easy to
scale to the desired level and all steps required for the expression of
antibodies, such as protein folding, assembly and glycosylation occur
naturally in plants.

With these facts in mind, a research group consisting of Dr. Akira Yano from
the Japanese National Institute of Public Health, and both Dr. Masataka
Takekoshi and Fumiko Maeda from the Tokai University School of Medicine in
Isehara, Japan, conducted a trial where a gene coding for human monoclonal
antibody against hepatitis B virus surface antigen was inserted into tobacco
plant cultures.

Once the researchers where able to confirm that the tobacco plant cultures
were producing the antibody, they purified the monoclonal antibodies and
tested for complement dependant cytotoxicity, as well as relative affinity
to the corresponding viral surface antigen?both of which, being two
important features of clinically beneficial antibodies.

After running the tests, the researchers found that the antibodies turned
out to be functionally equivalent to those gained from mammals, and were
also expressed in the quantities one would expect from a plant production
system.

Although these results, published in the Journal of Medical Virology, lead
to healthy optimism concerning the future of transgenic expression systems
and their clinical use, there still remains one caveat yet to be solved. It
may be necessary for example to "humanize" the plant's sugar, or
glycosylation patterns, in order to ensure they are accepted in the human
body. These patterns are added to proteins during synthesis, and are
different in humans and plants.

Once the question of glycosylation patterns has been addressed, antibodies
produced in transgenic plants should provide a safe and economical way of
fighting the many infectious diseases in the world today. Currently, Dr.
Yano and his team are working on finding interested investors and other
laboratories that are willing to collaborate with them on the continuation
of their work on this area.

To contact Dr. Akira Yano, send an e-mail to: akiray@niph.go.jp Mark
Finlayson is a Biology student at the University of Basel and a Science
Writer for Checkbiotech. Contact him at m.finlayson@stud.unibas.ch about
this article.

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