Science in Society Archive

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.

Article first published 05/03/09



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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