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ISIS Report 05/03/09
Magnifection, Safe Pharming or Doomsday Device?
Prof. Joe Cummins and
Dr. Mae-Wan Ho
Magnified infection makes other production methods obsolete
Biologicals
- recombinant proteins used as drugs, vaccines or antibodies – are found to
cause adverse side effects including death much more frequently than conventional
synthetic chemical drugs; and concern has been raised over their safety, not
only for patients undergoing treatment but also for the general public, as
these drugs are being produced in transgenic
plants grown in open fields [1] (see Biologicals,
Wonder Drugs with Problem, SiS 41).
Now it appears that there may be a safe and effective production method.
Recombinant proteins are produced in genetically modified microbes, human
or animal cells, or plants. In plants, recombinant proteins are made by four
methods: permanent modification of the nuclear genome, or the chloroplast
genome; and transient expression in the crop plant of modified plant viruses,
or modified Agrobacterium. The transient expression methods are capable
of producing higher levels of the recombinant proteins than permanent modifications
because many more copies of the recombinant genes are active in each plant
cell.
A combination of the transient expression methods is called magnifection.
Magnifection involves using modified plant virus vectors to modify Agrobacterium
strains that are in turn allowed to infect the crop plant in a mild vacuum.
The combined use of Agrobacterium and plant virus vectors results in
a large number of recombinant RNA virus particles entering the plant cells.
These recombinant RNA viruses epigenetically produce high levels of recombinant
proteins in a few days, and then decline. The crop plants transfected by the
modified viruses are used only once, producing no long term foot print on
the environment, it is claimed.
Magnifection was developed by Icon Genetics, a plant biotechnology
company. The process involves vacuum infiltration of whole plants with dilute
suspensions of agrobacteria carrying T-DNAs encoding RNA replicons. The bacteria
provide infection and systematic movement throughout the plant while the viral
vector provides short distance spread, amplification and high level expression.
The speed of the process is such that milligrams and grams of recombinant
protein are available in 3 to 4 weeks, and as much as 100 kg within less than
a year. Magnifection provides recombinant protein at up to 80 percent of
the total cell protein. The process is relatively inexpensive due to the speed
of production and high yield of recombinant protein that simplifies purification.
The whole process may be contained in a greenhouse; a one hectare greenhouse
is capable of producing 500 kg recombinant protein per
year. Previous viral vectors require a thousand times more space. The speed
at which large quantities of recombinant proteins can be produced means that
recombinant proteins can be tailor-made for diseases of individuals [2].
For the most
part, magnifection has been based on work with modified tobacco mosaic virus
(TMV) modifying tobacco plants. Two modified viruses, TMV and potato virus
X (PVX), were used to produce full size IgG antibodies in tobacco plants The
antibodies were produced in quantity in only 14 days after transfection [3], whereas it takes 6 to 12 months to produce the antibodies
in mammalian cell culture, or a year in stable transgenic animals [4]. Some
additional viral vectors have been developed for transient gene expression
such as cow pea mosaic virus, alfalfa mosaic virus,
tomato bushy stunt virus, plum pox virus and cucumber mosaic virus, all available
for delivery by Agrobacterium [5].
Investigators have developed a root absorption system for delivering suspensions
of agrobacteria modified with a TMV expression vector [6].
Agrobacterium-virus a doomsday device?
Magnifection
may sound like a safe alternative to growing pharm crops in open fields. But
we must be extremely wary of Agrobacterium vectors modified with virus
expression vectors. These doubly genetically modified and infectious bacteria
are bound to escape from any production facility to invade a wide range of
plants, causing pollution of food and feed crops with dangerous recombinant
proteins.
As
we have repeatedly warned since 2001, Agrobacterium is capable
of transfecting humans cells [7] (Common Plant Vector Injects Genes
into Human Cells, ISIS Report). An association
has been suggested between Agrobacterium and a painful skin disease
[8] Agrobacterium &
Morgellons Disease, A GM Connection?, SiS 39), and is now being investigated by the Centers for Disease
Control in the United States.
The Agrobacterium
bearing viral expression vectors with human genes should be thoroughly investigated for its effect on human and other
mammalian cells. Meanwhile, magnifection experiments should only be carried
out under the strictest confinement conditions equivalent to a category 3
microbiological laboratory for serious disease agents. The power and versatility
of genetic recombination should never be underestimated.
References
1. Cummins J. Biologicals,
wonder drugs with problems. Science in Society 41 (to appear).
2. Gleba Y, Klimyuk
V and Marillonnet S. Magnifection - a new platform for expressing recombinant
vaccines in plants. Vaccine 2005, 23(17-18), :2042-8.
3. Giritch A, Marillonnet
S, Engler C, van Eldik G, Botterman J, Klimyuk V and Gleba Y. Rapid high-yield
expression of full-size IgG antibodies in plants coinfected with noncompeting
viral vectors. Proc Natl Acad Sci U S A. 2006, 103(40), 14701-6.
4. Hiatt A and
Pauly M. Monoclonal antibodies from plants: a new speed record. Proc Natl
Acad Sci U S A. 2006;103(40),:14645-6.
5. Lico C, Chen
Q and Santi L. Viral vectors for production of recombinant proteins in plants.
J Cell Physiol. 2008, 216(2), 366-77.
6. Yang L, Wang
H, Liu J, Li L, Fan Y, Wang X, Song Y, Sun S, Wang L, Zhu X and Wang X. A
simple and effective system for foreign gene expression in plants via root
absorption of agrobacterial suspension. J Biotechnol. 2008, 134(3-4),
320-4
7. Cummins, J.
Common plant vector injects genes into human cells Institute of Science in Society http://www.i-sis.org.uk/Agrobacterium.php
8. Ho M-W and Cummins
J. Agrobacterium and Morgellons Disease, A GM connection? Science in Society 38, 33-36,
2008.
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