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

Researchers from Icon Genetics and Bayer BioScience developed a novel way to
produce healthcare drugs called biomedicals quickly and efficiently in
plants, October 2006
by Daniela Kenzelmann, Checkbiotech.

An increasing number of reports demonstrate that biomedicals like
therapeutic antibodies or vaccines can be inexpensively produced in plants.
Normally, the production of such a agent requires the generation of a
genetically modified plant line, which is a time-consuming process.

Dr. Yuri Gleba and his coworkers have found a shortcut to produce antibodies
with a special genetical tool called transient expression system, which
allows researchers to introduce desired genetic material into an organism.
This means that the genes which encode the antibody to be produced are not
inserted into the genome of the plant, but instead viruses are used as
vectors to bring the antibody-genes into the plants.

The major problem that the researchers had to solve is that two genes are
necessary to build a full antibody, because it is composed of two subunits
named the heavy and the light chain. Previous attempts to pack both of these
genes together in one virus were unsuccessful in terms of antibody
production levels.

Therefore, Dr. Gleba?s group had the idea to use two viruses carrying one of
the antibody-subunits each. Normally, two viruses of the same kind would
compete, meaning that one cell can only be infected with one virus. For
antibody production however, it is required that both viruses are present in
the same plant cell. The researchers achieved this by using two different
viruses which were known to be non-competing: tobacco mosaic virus and
potato virus X.

First, the researchers had to modify the viruses that they would carry one
of the antibody genes. Secondly, tobacco leaves were co-infected with the
two artificial viruses. The last step involved purification of the
antibodies from the leaves and their characterization. Dr. Gleba?s group
showed that antibody subunits as well as correctly assembled antibodies
accumulate in the leaves in less than 10 days. Equally important is that
they showed that the antibodies recognized their target antigen.

To make sure that these modified viruses do not escape and convert normal
plants into antibody-plants, the researchers handicapped the viruses in a
way that they can only infect plants with the help of a special bacterium.
This will prevent them from crossing with other plants and passing on their
new genetic material.

Dr. Gleba?s results are a proof of concept that two non-competing viruses
can be used to produce therapeutic antibodies in plants without the need to
create transgenic plants. The procedure has potential for unlimited scale-up
for industrial production of biomedicines and its rapidity and versatility
would allow manufacturers to respond to suddenly increasing demands.
Additionally it could speed up research, because antibodies are also
important tools for scientists.

Future work will be to further improve the antibody production levels, for
example to determine the ideal ratios of both viruses for full antibody
assembly. Additionally, Dr. Gleba has considered giving cells the ability to
produce factors which facilitate the assembly of the antibody. As a next
step it will be crucial to prove that antibodies produced by viral infection
are equally efficient in treating diseases than conventionally produced
antibodies.

Daniela Kenzelmann is a Science Journalist for Checkbiotech and is writing
her PhD at the Friedrich Miescher Institute in Basel, Switzerland. Contact
her at daniela.kenzelmann@fmi.ch

Giritch et al.Rapid high-yield expression of full-size IgG antibodies in
plants using noncompeting viral vectors. PNAS, 2006

[www.ncbi.nlm.nih.gov]
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