Transgenes are foreign or modified genes, added to animals or plants to create a transgenic organism. These organisms are genetically engineered to alter the expression of a gene or genes; often to improve food production or model human diseases.
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Agriculture is perhaps the most obvious application of genetic modification, with over 160 “New Plant Varieties” registered in the FDA inventory. Improved resistance to pests and disease, as well as increased tolerance to herbicides, are among the most common modified traits. But, developers can also modify traits to increase crop yield, improve tolerance to environmental stressors and enhance the nutrient composition.
In 1999 the Golden Rice Project was introduced; they aimed to provide a sustainable biofortification option to populations where both vitamin A deficiencies and dependencies on micronutrient-poor carbohydrate foods are commonplace. By adding two genes, developers were able to “turn on” the machinery that the rice plant possesses to synthesize β-carotene in the grain, a carotenoid with provitamin A activity.
Recombinant DNA strategies optimized for plants utilize bacterial plasmids to transfect cells from leaf cuttings. These bacterial plasmids contain the desired transgenes and marker genes to allow selective growth of transfected cells in culture. By using a selection medium during incubation, developers can ensure only transfected cells survive and proliferate.
While this helps developers efficiently produce transgenic plants, it has not come without controversy. The commercialization of transgenic organisms has sparked concern for various reasons, including the use of selection genes. These selection genes/markers are used to distinguish successful uptake of transgenes; they can include visual changes or resistance to antibiotics.
Marker genes that carry antibiotic resistance have been termed environmental pollutants, with concern surrounding the risk of horizontal gene transfer. While the risk of horizontal gene transfer from transgenic organisms is low, these events can compromise the therapeutic value of the antibiotic and introduce invasive species to the natural environment.
Transgenic plants in medicine
As well as their potential to improve food security, transgenic plants can be used to produce biopharmaceuticals. Edible vaccines utilize transgenic plants in this way. By either direct or vector-mediated gene delivery, the plant can be developed to express particular disease antigens.
The edible vaccines produced from these plants primarily activate the mucosal immune response, triggering both the innate and adaptive arms of the immune system. This provides an easier mode of administration and a more cost-effective option to traditional vaccines.
Perhaps unsurprisingly, edible vaccines have been the subject of skepticism; combining two topics considered to be “controversial”, vaccines and genetically modified organisms. While their safety is often debated, edible vaccines have been approved by the National Institute of Allergy and Infectious Diseases since 1998.
Edible vaccines offer a more sustainable and accessible alternative to traditional vaccines, particularly in countries where proper storage and administration are not available. As of 2020, clinical trials for edible vaccines against Hepatitis B, Cholera, Influenza, Rabies, and E. Coli were being conducted.
Using transgenic organisms to create disease replicas
Recombinant DNA technology has revolutionized health care beyond the production of vaccines. Genetically modified animals are often used to help better understand the underlying mechanisms of an individual's disease.
By introducing the genes associated with the disease phenotype, it is possible to create a transgenic organism that mimics the condition. These animals can then be used to gain a deeper understanding of the cellular and molecular basis of disease, as well as aid in screening for efficacious treatment options.
Mice are perhaps the most extensively used to create transgenic and gene knockout models, providing the foundation for genomic studies and understanding of disease aetiologies. By introducing the target transgene to mouse embryonic stem (ES) cells, injecting it into an early embryo, and transferring it into a pseudopregnant mouse, developers can breed mice with the target gene in germ-line.
To ensure non-random insertion or deletion of the target gene, methods utilizing homologous recombination have been developed. The CRISPR-Cas system is one of the most widely known examples, with a variety of applications. A guide RNA within the Cas protein targets it to a particular location in the genome; when the guide RNA binds the correct sequence of DNA and the PAM sequence is present, the Cas protein creates a double-strand break.
The CRISPR system will then repair the DNA using the transgene as its template. This system can also be modified to act as a transcription activator or repressor. By inactivating the Cas proteins endonuclease activity, the CRISPR system can be used to direct accessory functions to their target in the DNA efficiently.
Transgenic organisms have proven powerful tools in genetics and genomics, allowing for a better understanding of gene functions and the genes associated with disease phenotypes. As DNA sequencing becomes more affordable and available, the potential to create an in vivo replica for each individual's condition could improve precision medicine for many.
Continue reading about genetically modified food here.
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