www.checkbiotech.org ; www.raupp.info ; www.czu.cz

Using plants to produce useful proteins could be an inexpensive alternative
to current medicine production methods, January 2007.

Researchers from the Flanders Interuniversity Institute for Biotechnology
(VIB) at Ghent University have succeeded in producing in plant seeds
proteins that have a very strong resemblance to antibodies. They have also
demonstrated that these antibody variants are just as active as the whole
antibodies that occur naturally in humans. By virtue of their particular
action, antibodies are very useful for therapeutic and diagnostic
applications. From this research, it is now also clear that these kinds of
antibody variants can be used in medical applications and that it is
possible to produce them in the seeds of plants, which can have enormous
advantages over conventional production methods.

Production of biotech medicines
A large number of today?s medicines are made with the aid of biotechnology
(and this number should only grow in the future). To do this, scientists use
genetically modified bacteria, yeasts, or animal cells that are able to
produce human proteins. These proteins are then purified and administered as
medicines. Examples of such proteins are antibodies, which can be used, for
instance, in the treatment of cancer. The conventional methods for producing
antibodies work well, but they are expensive and have a limited production
capacity. The high costs are primarily due to the need for well-equipped
production labs and to the labor-intensive upkeep of the animal cells, which
are needed as production units.

Plants: a possible alternative?
For a number of years now, the VIB researchers in Ghent - Bart Van
Droogenbroeck, Ann Depicker and Geert De Jaeger- have been searching for
ways to have plants produce useful proteins efficiently. Plants do offer a
lot of advantages over conventional production methods. Because production
with plants doesn?t require expensive high-tech laboratories, scientists
anticipate that, by working with plants, production costs will be 10 to 100
times lower. Another important advantage is that large-scale production is
possible without having to make additional investments in expensive
fermentors.

A good yield guaranteed
Several years ago, Geert De Jaeger and his colleagues succeeded in achieving
a high yield of an antibody variant in plants, which had been very difficult
to do up to that time. The trick the researchers used was to modify the
plants in such a way that they would produce the antibody variant in their
seeds. With their special technique, the scientists succeeded in producing
seeds in which the desired protein is good for more than one third of the
total protein amount. This is a huge proportion compared to other systems -
normally, scientists succeed in replacing only 1% of the plant?s proteins by
the desired protein.

Plant seeds are especially attractive as production units. In addition to a
high production capacity, they offer other important advantages over other
parts of the plant. The seeds can be stored for a long time without losing
the produced protein?s effectiveness, so that a reserve can always be kept
on hand. This means that the proteins can be isolated from the seeds at the
moment that they are actually needed. With production in leaves, for
example - or with conventional production methods - such lengthy storage is
not possible: the protein must be isolated immediately after production. So,
production in plant seeds provides the clear advantage of timely processing.

High production of an efficient antibody variant
The antibody variant that has been produced by Geert De Jaeger and his team
has a very simple structure and has only one binding place for a particular
substance. Bart Van Droogenbroeck and his colleagues, under the direction of
Ann Depicker, are now showing that it is also possible to produce more
complex antibody variants in large quantities in the seeds of the
Arabidopsis plant. Over 10% of the proteins in the seeds of these plants are
the desired antibody variant. As is the case with whole antibodies, these
more complex antibody variants have two binding places for a specified
substance. This close similarity to whole antibodies makes these antibody
variants extremely useful for therapeutic and diagnostic applications.

However, the production of proteins in plants is completed in a different
way than in humans. Therefore, to be certain that this different completion
process does not affect the effectiveness of the potential medicine; the
scientists have subjected the action of the antibody variant to an
exhaustive battery of tests. These laboratory tests have shown that the
antibody variants produced in plants are just as effective as whole human
antibodies in protecting animal cells against infection with the Hepatitis A
virus.
This is a significant step forward in making protein production in plants a
real alternative to current production methods.

Scientific publication
The research appears on line on the website of the authoritative magazine
PNAS this week ?Aberrant localization and underglycosylation of highly
accumulating single-chain Fv-Fc antibodies in transgenic Arabidopsis seeds?,
Van Droogenbroeck et al., PNAS, 2007.

Related publication
?Boosting heterologous protein production in transgenic dicotyledonous seeds
using Phaseolus vulgaris regulatory sequences?, De Jaeger et al., Nature
Biotechnology, 2002.

Funding
This research has been funded by VIB, Ghent University, and the 6th
Framework Programme of the European Union via the Pharma-Planta Consortium.

Given that this research can raise a lot of questions for patients, we ask
you to please refer questions in your report or article to the email address
that VIB makes available for this purpose: patienteninfo@vib.be. Everyone
can submit questions concerning this and other medically-oriented research
directly to VIB via this address.

VIB, the Flanders Interuniversity Institute for Biotechnology, is a
non-profit research institute in the life sciences. Some 1000 scientists and
technicians conduct strategic basic research on the molecular mechanisms
that control the functioning of the human body, plants, and micro-organisms.
Through a close partnership with four Flemish universities - Ghent
University, the Katholieke Universiteit Leuven, the University of Antwerp,
and the Vrije Universiteit Brussel - and a solid investment program, VIB
unites the forces of 65 research groups in a single institute. Their
research aims at fundamentally extending the frontiers of our knowledge.
Through its technology transfer activities, VIB strives to convert the
research results into products for the benefit of consumers and patients.
VIB also develops and distributes a broad range of scientifically
substantiated information about all aspects of biotechnology. More info at:
www.vib.be

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