12 December 2014

Biofactory plants

Alice Vyacheslavova, Post-science5 facts about Transgenic Plants, Vaccine Production


and the production of proteins for medical purposes

A relatively new direction in the creation of transgenic plants is the use of plants as biofactory plants. What does it mean? This means that various proteins of medical origin and purpose, various preparations for vaccination, oils, vitamins and much more will be developed in plant cells.

1. Advantages of using plantsWhy are plants biofactories, why are they better than existing systems?

Let me remind you that today many medical proteins and pharmaceuticals are produced in yeast, in bacterial cells, as well as in mammalian cells. To begin with, plant biofactories will be very cheap, especially compared to mammalian cells. Secondly, since plants are in biological classification at different levels with humans, the danger of getting some kind of infection for humans is minimized, unlike again mammalian cells, which may contain animal viruses, may contain various prions and much more, which is very dangerous for humans. This does not happen in plants, and even if some plant virus suddenly turns out to be there, it will not cause any harm to humans. Thirdly, plant systems have, like all eukaryotes, the ability to post-translational modifications. What does it mean? Many proteins after formation need various modifications, that is, for example, in hanging additional groups or in some special folding. In yeast, such modifications are very difficult, and in bacterial ones, in principle, they are impossible, because bacterial systems are prokaryotes that do not have the ability to post-translational modification. There are such opportunities in plant cells, and this is another plus in favor of plants for developing medical proteins.

2. Protein production in plantsFor the first time, the production of human protein in plants happened in the late 80s, and it was human growth hormone.

It was developed in tobacco and sunflower. It was, of course, a sensation, a triumph, and this event was the beginning of a whole boom in the production of various human and animal proteins in plants. For example, to date, interferon of various types is successfully developed in tobacco plants, potato plants, and lettuce: alpha, beta, gamma. Medical proteins such as somatotropin, erythropoietins, immunoglobulin of various types are being developed, plus milk protein casein is being developed, various elastic proteins such as elastin, collagen and many others are being developed. As you can see, the range of use of the produced proteins is huge. Plus, the production takes place not only in model objects, such as tobacco, but also in agricultural crops — lettuce, tomatoes, potatoes and many other crops. The development of such crops leads to the fact that we can use these crops as edible vaccines, which again is a huge advantage. What does "edible vaccines" mean? This means that in some edible part of the plant, whether it is a lettuce leaf or a potato tuber, a certain antigen or a certain epitope to some virus is being developed, or that some antibodies may be developed in this part of the plant, which also leads to a positive immune response. What is most interesting, these studies have been conducted and are still being conducted, since this direction is quite new, and positive results have been obtained to date. In addition to the fact that plants actually produce effective medical proteins that meet all chemical standards and cause various immune responses, studies have already been conducted on volunteers who ate raw potatoes, and an immune response was detected during the analysis of their blood, that is, antibodies were formed.

3. Practical applicationIt is worth emphasizing that this topic is quite promising, and even now, despite its young age, it comes out of exclusively laboratory research and is applied in practice.

For example, the American company Sigma Aldrich produces such medical proteins as trypsin and many others that are produced in corn. That is, these are recombinant proteins. Anyone can order them, buy them, purchase them for their research and practical needs. In addition, a good indicator for biofactory plants is that such industrial monsters as Icon Genetics, Bayer, which produce many medicines, and many leading scientific institutes that already produce drugs for practical use, are actively engaged in this topic. As an example of the use of edible vaccines in practice, we can already cite such cases as the production of two antigens in potatoes. One of them encodes the B subunit of E. coli (E. coli). The second gene expressed in potatoes encodes the norovirus capsid. These two diseases are quite dangerous, and they are intestinal diseases. In fact, if we speak openly, intestinal diseases occupy one of the leading positions in the world in terms of morbidity, especially, of course, in third world countries. The obtained two modified potatoes carrying two antigens were tested with the participation of volunteers, and it was shown that when volunteers consume raw potatoes, antibodies are formed in their blood, and, accordingly, an immune response is triggered, which indicates the phenomenal ability of plants to produce not only their genes, to include not only their genes and to produce some vitamins of natural origin, but also to develop externally introduced proteins, to include externally introduced genes, which is a remarkable discovery.

4. Vaccine productionThe range of applications of biofactory plants for creating a variety of vaccines is huge, because each disease uses its own vaccine.

That is, for example, for diseases of the upper respiratory tract, we must make an appropriate vaccine. There is a flu disease so-and—so - a vaccine for this flu. Avian flu is already a vaccine against avian flu. That is, we cannot make a universal vaccine, so we have to create plants and not only plants - now in pharmacology, when a new disease appears, the development of a drug for this disease or the development of a vaccine to prevent the recurrence of the disease immediately begins, this is a rather complicated process. But, what is interesting for plants, we can develop not one vaccine, but two, three, four in one plant organ, for example, in a tuber. This is due to the use of those constructs in which we embed certain genes. That is, we have some kind of structure consisting of DNA molecules, we can embed in it one epitope for the upper respiratory tract virus, one epitope for such-and-such flu, for another type of flu, and then move all this into a plant, into a tuber, and thus in one tuber we have we will already be expressing such a polyvalent vaccine against many diseases. Again, this is, unfortunately, a non-universal vaccine, but as a way out, in particular for use in veterinary medicine. As you know, for animals, any injection, any intervention, taking a blood test is a rather complicated procedure, and it is too traumatic for an animal. In some cases, this may affect the "yield", so it seems to me that the use of such edible vaccines produced in forage grass will be an excellent way out in order not to injure the animal and, possibly, increase yields in some cases.

5. Complexity of the procedureDespite all the advantages that surround biofactory plants, namely edible vaccines, of course, they also have their drawbacks.

For example, despite the presence of posttranslational modifications in plants, they may differ from those for animal cells. Because of this, animal proteins produced in plants may be less effective or have no effect at all. In addition, for biofactory plants, these are difficulties in some cases for transformation, for the transfer of genetic material into plant cells. For example, now we are working with tobacco, potatoes — with a number of agricultural crops — this procedure has been worked out for them. For the spectrum of other plants, such a procedure has not yet been worked out, and it is the development of the scheme that is quite complex and long enough, and it is not a fact that it will work. Therefore, it seems to me that the question of using plants as biofactories, despite the attractiveness of this idea, is still open. This issue is being dealt with — we will monitor the development.

About the author:
Alisa Vyacheslavova – Candidate of Biological Sciences, Junior Researcher of the Plant Genomics Group of the Institute of General Genetics of the Russian Academy of Sciences.

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