Origin and history of medical genetic engineering
1865: Gregor Johann Mendel explores the mechanisms of inheritance using yellow and green peas, laying the foundation for understanding the inheritance of traits.
1953: James Watson and Francis Crick publish the double helix model of DNA.
1973: Foreign DNA can be successfully integrated into the genome of a microorganism for the first time.
1977: For the first time, a human protein is produced in the common intestinal bacterium Escherichia coli.
1977 Sanger and Coulson publish their method for DNA sequencing.
1982: Human insulin is approved as the first genetically engineered drug.
1990: The Human Genome Project is launched with the aim of sequencing the complete human genome.
1990: The world's first gene therapy is performed: A little girl in the USA is injected with genetically modified cells with the aim of replacing the defective gene that had led to an immune system disorder in her with an intact version of the gene.
2010: For the first time, a completely synthetic genome is created and integrated into an empty bacterial cell.
2012: The CRISPR-Cas9 system for genome editing is discovered and published.
New drugs thanks to genetic engineering
The genetic engineering of vital medicines is becoming increasingly important. Almost every second newly approved active ingredient is produced using genetic engineering. Taken together, over 290 such drugs with more than 240 active ingredients are currently approved in Germany1. These include human insulins and biotechnological drugs for cancer, autoimmune diseases, metabolic and coagulation disorders. Vaccines against cervical cancer and hepatitis B are also produced using genetically modified organisms (GMOs). GMOs have foreign genes integrated into their genome, allowing them to produce certain proteins in greater quantities than they normally do. For example, it is possible for bacteria to produce the human version of insulin, human insulin.
Some diseases, instead of being treated with genetically engineered pharmaceuticals, are treated with gene therapy. In gene therapy, foreign genes are integrated directly into the DNA of the patient's cells. In most cases, the aim is to replace a defective gene with its intact version. However, gene therapy of germline cells (eggs and sperm) is prohibited by law in Germany to prevent the alteration of DNA from being passed on to offspring2.
In addition to treatment, genetic engineering can also contribute to the diagnosis of diseases and genetic defects. For example, so-called DNA chips can be used to test whether a patient has an increased risk of hereditary breast cancer
Switching off genes specifically
To determine the function of specific genes and study diseases, scientists can specifically switch off genes. They can intervene directly in the genome of a living experimental organism (in vivo) or alter the DNA of individual cells in culture (in vitro). To silence a gene (knock-out), cells are treated with specific enzymes called endonucleases. These cut the genome at the specific site. The breaks in the DNA double strand are usually reconnected in animal and human cells by the process of non-homologous end joining (NHEJ). In the course of this repair process, parts of the original sequence are lost, permanently affecting the function of the gene.
Viruses as tools of genetic engineering
Hereditary diseases are caused by mutations in the DNA, as a result of which certain proteins are not formed or are formed incorrectly. To compensate for this deficit, intact genes can be introduced into the diseased organism. Although it may sound contradictory at first, this is precisely what is possible with the help of viruses. By their very nature, viruses need a host to replicate their own genetic information. Some viruses even go so far as to insert their genes into the genome of their host. Today, such viruses are used as "vectors" for genetic engineering. To do this, the virus genome is simply replaced by the specific DNA sequence that is to be introduced into an organism or cell, and the "host" is then infected.
Specific integration of foreign genes
While viruses can efficiently introduce foreign genes into an organism's genetic code, the exact site of integration often cannot be controlled. For site-specific integration of foreign genes, the genome must first be dissected by an endonuclease at the specified site. This can be done particularly quickly and cheaply using CRISPR-Cas9 technology. In this genome editing method, named Breakthrough of the Year 2015 by Science magazine, an attached RNA navigates the endonuclease Cas9 to the target sequence. This "guide RNA" can be very easily customized by researchers to target a variety of different sequences.
Once the endonuclease has cut the double helix, a foreign DNA segment can be incorporated into the cleavage site. A prerequisite for successful integration is that the sequence at the ends of the foreign DNA is exactly opposite ("homologous") to the break site in the genome. These homologous regions bind to each other and the foreign DNA is incorporated as a bridge between the two break ends. This mechanism is called homologous recombination. This makes it possible to design recombinant DNA molecules that have DNA sequences from different organisms, which do not occur in nature. However, most cells do not absorb naked DNA on their own. This is ensured by the cell membrane, which is a natural protective barrier that regulates transport into and out of the cell. Researchers, however, can use voltage, ultrasound or heat shock to affect the permeability of the cell membrane, allowing the cells to take up the foreign molecules.
Genetic engineering plays an important role in medical care, providing the basis for many innovative drugs, therapies, and preventive care. For example, the CRISPR-Cas9 method can be used to specifically tailor DNA and then modify it. This genetic engineering method can be used in almost all living cells and organisms. This opens up new possibilities for the fight against AIDS, cancer and a range of hereditary diseases.
