Healing hereditary diseases by cutting defective genes from the genome and replacing them with healthy ones: that is the principle of genome editing, which in principle has become possible thanks to the gene-shearing Crispr. A team from the Broad Institute in Cambridge, USA, now reports in Nature magazine (Anzalone et al., 2019) that the method has evolved. This could one day enable up to 89 percent of all known human genetic disorders to be corrected.
So far, such gene modifications to humans for ethical reasons are not allowed for either studies or as therapy because of possible side effects. The current study is therefore about basic research, but also about new possibilities for green genetic engineering. For example, genome editing can be used to grow plants whose genetic material has changed so that they are resistant to certain pests.
Less side effects and more efficiency
Prime researchers call the researchers their method based on the idea of Crispr / Cas9 gene scissors. It is an intelligent further development of the technology, said Jan Korbel from the European Molecular Biology Laboratory in Heidelberg journalists of the German Science Media Center (SMC) ( see box ). "The Prime Editing performs unlike Crispr / Cas9 by the targeted use of a specific enzyme no fragmentation of the genome." That's why there are fewer unwanted mutations than Crispr / Cas9. "This can be very important for future applications in medicine."
Indeed, the US research team reports that Prime Editing very precisely exchange, insert (insert) or delete (deletion) single DNA components (bases) or create changes that combine these capabilities. Overall, this results in fewer uncontrollable side effects, such as changes in locations of the DNA that were not the target of the gene slice, so-called off-target effects. The new application is also more efficient than previous genome editing methods.
In four different human cell lines as well as in nerve cells of mice, the scientists used Prime Editing to perform more than 175 genetic modifications, including targeted introduction, deletion and all twelve known forms of exchange. In addition, they corrected the primary genetic causes of two hereditary diseases: sickle cell anemia and Tay-Sachs disease. As the team in Nature reported, this succeeded in cells efficiently and with few side effects.
Crispr - How the new universal tool of genetic engineering works Affordable, easy to handle and extremely effective: Crispr is revolutionizing genetic engineering. The genome of all living things can thus be arbitrarily shaped, as the video shows.
Thus, the new method is not free of risks, says Jan Korbel. It could also produce hard-to-measure mutations. "Such by-products should be excluded in the future before the technology can be safely used in medicine, but we're not that far yet."
Experiments with human genetic material caused horror
The fact that genetic engineering has not yet been tried on humans, however, is not quite true: In 2018, the Chinese researcher He Jiankui announced that he had applied the Crispr method to human embryos. They removed and replaced a specific gene segment from the genome, which made the children immune to HIV. A woman gave birth to the first twins after artificial insemination, whose genetic material was changed with Crispr / Cas9. The case was convicted by international experts. The scientists, who claim to be the discoverers of gene-shearing, demanded a worldwide moratorium not to use them in the human germline. In China, the researcher has been under criminal investigation since its publication, and He Jiankui has had to stop his research.
However, individual researchers such as the Russian microbiologist Denis Rebrikow still want to genetically alter humans in the future. His plan, provided that he officially gets the green light: He wants to enable children deaf parents can hear themselves. But Rebrikow wants to intervene long before birth with Crispr / Cas9 in their genome. In an interview with ZEIT ONLINE he asked the provocative question: "What is better: to make a therapy or healthy babies?"
This will greatly accelerate modern (plant) breeding. Jens Boch, plant biotechnologist
On the other hand, Prime Editing could possibly be easier to cultivate in plant breeding. "The new method is a very useful middle ground of the previous possibilities," said the biotechnologist Jens Boch of the Leibniz University in Hanover the SMC. With it very quickly precise changes for useful properties in important cultivars could be introduced. "This will greatly accelerate modern breeding." In Europe, however, Prime Editing is covered by the Genetic Engineering Act and will therefore not be used for the European market.
However, the technology should not be overstated, said Holger Puchta of the Karlsruhe Institute of Technology. Although it could help to obtain more easily disease-resistant plants or, for example, gluten-free plant products. Of course, that has to be tested first. " In addition, the risk of prime editing always depends on the application. While it is important in medicine to exclude any kind of additional genome changes as the desired, this is not so relevant in green genetic engineering. Such questions played a minor role there, "as breeding has been tolerating thousands of undirected genomic changes for 70 years". These also occur naturally, without the human intervention in the laboratory.
Read more about the Crispr-Genschere and where it is already used today, read in our focus "Man recreates himself".