By Cyrill Götz, Checkbiotech
Due to increasing safety rules and regulations, the cost to develop
new drugs is constantly out pacing profitability. To help reduce this trend,
a tiny plant may be a promising system to generate adequate amounts of high
quality biopharmaceuticals.
So far microbial and mammalian cells are the two systems which are
used to generate biopharmaceutical drugs. Microbes are used because of the
high product yields and the mammalian cells are favored because the end
product is more readily comparable to what you find in humans.

The moss Physcomitrella patens has stepped into the limelight, because
it has some important advantages over microbial and mammalian production
systems. For Dr. Eva Decker, from the faculty of Biology at the University
Freiburg, Germany, the moss plant is favorable because it can easily be
genetically modified, which allows researchers to quickly generate new moss
plants that can produce a biopharmaceutical of interest.

Another advantage of using moss is it can be used in production
systems known as bioreactors that minimize the need for human interaction,
augment the amount of product and increase safety.

When setting out to create a moss bioreactor, the first step is to
insert the gene into the moss genome that will produce the desired drug.
What is also needed are efficient secretion signals. These signals will
determine the path that the protein is going to take through the cell. Two
very important stations on this path are the Endoplasmic Reticulum and the
Golgi Apparatus. These two cell compartments are responsible for many
modifications of the freshly synthesized protein, for example the attachment
of sugar residues.

These modifications are a very important step in producing
biopharmaceuticals in moss. Their structure determines if the moss produced
protein will have the same characteristics and functionality that it did
when produced in humans.

A critical difference between the human- and the plant derived
proteins are specific sugar residues. Deviations from human sugar residues
could provoke an immune response which would render the biopharmaceutical
drug useless or even dangerous.

To overcome the obstacle of sugar residues, Dr. Decker's group has
removed the genes responsible for plant-specific sugar residues from the
moss genome and replaced the genes with human ones. This ensures that the
final product will more closely resemble the human produced
biopharmaceutical. Dr. Decker told Checkbiotech that the next stages of
research will focus on the further improvement of the human-like
modifications of the proteins.

So far moss seems to be an attractive system to produce
biopharmaceuticals, because it has economical and biological advantages.
There have been for example positive results in the production of
antibodies, which is one of the most interesting group of biotech drugs.
Antibodies which were synthesized and folded in genetically modified moss
strains showed 40-fold higher activity than the antibodies produced in
mammalian cells.

These results demonstrate that with moss, researchers may have found a
better production system for biopharmaceuticals. In the future, when you see
moss growing on a tree in the woods, your first thought might be how that
plant has changed the medical world and not that it tells you were north and
south is.

Cyrill Götz is a Science Writer for Checkbiotech in Basel,
Switzerland, and is currently studying biology at the University of Basel.

Source: Eva Decker and Ralf Reski. Current achievements in the
production of complex biopharmaceuticals with moss bioreactors. Bioprocess
and Biosystems Engineering, 2007.


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