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(Note: This article is the 2nd in a 3 part series on Genetic Engineering. To read the 1st part, please click here. )
Written by Paul Melamud - Validation Manager, QPharma
Introduction
When we refer to organisms that are “transgenic”, this means that DNA from one species has been inserted into another species for expression. Gene transfer between organisms of the same species is often called “intragenic”, and that between species that are sexually compatible is called “cisgenic”. These latter types are widely known; for example, Gregor Mendel selectively mated pea plants to study genetics in the 1800s, and for another, dog breeders continually attempt to create dogs that perfectly match the personality and stature conformation standards set forth by the Americal Kennel Club. These also comprise the basics behind the theory of evolution.
The first transgenic products were plants, made primarily to create disease-resistant and higher-nutrition foodstuffs (refer, for example, to Hope, a traditionally-produced (non-recombinant) hybrid that saved American wheat crops in the 1930s). In the 1980s, the first true Genetically Engineered or "GE" plants (tobacco) were made with inherent insecticidal and herbicide-resistant properties. These days, there are many bright prospects for products being dubbed “plantigens” and “plantibodies” that will contribute to public health at large, if introduced into standard crops. What may be surprising to learn, then, is that there are not yet any FDA-approved, plant-biopharmed pharmaceutical products.
Processes
There are two main processes that are used to genetically engineer plants for traits such as herbicide resistance. Similar techniques would be employed to cause the plant to express phenotypes with human therapeutic use. The first process, bacteria-mediated transformation, is accomplished with a bacterial vector, most commonly Agrobacterium tumefaciens, a plant parasite that can cause tumors by injecting DNA into host cells. It is this unique mechanism that scientists have harnessed to deliver DNA of their choosing for expression in plants. The second process, biolistic transformation, involves coating pellets of metal, such as tungsten or gold, with DNA and literally firing them into plant cells so that they lodge in the nuclei. Once there, the DNA separates from the metal and becomes integrated with the host DNA for expression.
These two processes are illustrated below, one diagram from McGraw-Hill Higher Education and the other from BBC News (see links below image for references).
Introduction
When we refer to organisms that are “transgenic”, this means that DNA from one species has been inserted into another species for expression. Gene transfer between organisms of the same species is often called “intragenic”, and that between species that are sexually compatible is called “cisgenic”. These latter types are widely known; for example, Gregor Mendel selectively mated pea plants to study genetics in the 1800s, and for another, dog breeders continually attempt to create dogs that perfectly match the personality and stature conformation standards set forth by the Americal Kennel Club. These also comprise the basics behind the theory of evolution.
The first transgenic products were plants, made primarily to create disease-resistant and higher-nutrition foodstuffs (refer, for example, to Hope, a traditionally-produced (non-recombinant) hybrid that saved American wheat crops in the 1930s). In the 1980s, the first true Genetically Engineered or "GE" plants (tobacco) were made with inherent insecticidal and herbicide-resistant properties. These days, there are many bright prospects for products being dubbed “plantigens” and “plantibodies” that will contribute to public health at large, if introduced into standard crops. What may be surprising to learn, then, is that there are not yet any FDA-approved, plant-biopharmed pharmaceutical products.
Processes
There are two main processes that are used to genetically engineer plants for traits such as herbicide resistance. Similar techniques would be employed to cause the plant to express phenotypes with human therapeutic use. The first process, bacteria-mediated transformation, is accomplished with a bacterial vector, most commonly Agrobacterium tumefaciens, a plant parasite that can cause tumors by injecting DNA into host cells. It is this unique mechanism that scientists have harnessed to deliver DNA of their choosing for expression in plants. The second process, biolistic transformation, involves coating pellets of metal, such as tungsten or gold, with DNA and literally firing them into plant cells so that they lodge in the nuclei. Once there, the DNA separates from the metal and becomes integrated with the host DNA for expression.
These two processes are illustrated below, one diagram from McGraw-Hill Higher Education and the other from BBC News (see links below image for references).
 |
| http://www.mhhe.com/biosci/pae/botany/botany_map/articles/article_03.html |
 |
| http://news.bbc.co.uk/2/shared/spl/hi/pop_ups/03/sci_nat_how_a_plant_is_genetically_modified/html/3.stm |
There are a few other, less common methods that are used, including electroporation (electrically inducing transient holes through cell walls and membranes through which DNA can be introduced) and viral transduction (analogous to the bacterial vector transformation method). Electroporation is illustrated below.
 |
| http://www.inovio.com/images/IMG_how_ep_delivers.gif |
Any of these methods can be used to attempt to transform millions or billions of cells – and that’s a good thing, because successes may occur as rarely as one in a billion. Scientists can’t look at every cell, so they have developed techniques (as illustrated above) that can easily distinguish the successes and allow for their isolation. The above method illustrates the use of a “selective agent” or “selectable marker,” which means that only the successfully transformed cells will survive exposure to the negative stimulus (i.e. the herbicide against which the genetic change would protect). Another method is coupling the desired gene with a second one that will provide a “screening marker”, which can be observed by a scientist; an example would be a gene that causes a cell to fluoresce under UV light, which would indicate successful integration of the DNA that was introduced.
Regulation
We can all appreciate how relatively new such products are, and that the process of development, testing, and eventually clinical trials and/or field studies to bring these products to the market would still be underway. There are a few other reasons, though, that I think explains why we don’t see such products on the market yet.
One reason behind this is that...
Regulation
We can all appreciate how relatively new such products are, and that the process of development, testing, and eventually clinical trials and/or field studies to bring these products to the market would still be underway. There are a few other reasons, though, that I think explains why we don’t see such products on the market yet.
One reason behind this is that...
