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