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The Nobel Prize in Chemistry was awarded today to Emmanuelle Charpentier and Jennifer A. Doudna “for developing a genome editing system.” The CRISPR / Cas9 system, developed by the two researchers, has provided a powerful new solution for changing the DNA of animals, plants, and other microorganisms with unprecedented precision. In recent years, this system has allowed the development of new cancer therapies and could make possible the cure of various inherited diseases.
A huge war
Even if we don’t realize it, since life has existed, bacteria and viruses have waged an all-out war, giving them good reason. Bacteriophages (or phages), for example, are particular viruses that search for bacteria. It is estimated that alone they kill about 40 percent of the trillions of bacteria that live in the oceans each day (billions of new bacteria are formed every day).
Once they come into contact with the bacteria, the phages inject their own genetic material into them, turning them into tiny factories that will produce other viruses, which in turn infect other bacteria. Unlike more complex organisms with advanced immune systems like ours, bacteria have fewer defenses and almost always do not resist.
Sometimes, however, it happens that some bacteria are able to resist attack by bacteriophages. When this happens, they store part of the genetic material of the virus in its genetic code, in a kind of catalog that researchers call CRISPR, of short palindromic repeats grouped regularly interspaced (Short palindrome repeats grouped and separated at regulated intervals).
If you later come into contact with a virus again, the bacterium makes a copy of the genetic material it had stored and transmits it to a protein called Cas9. This goes to work and searches for DNA fragments within the bacteria and compares them to those in the archive, to understand if a virus is present. If it detects a match, it cuts the genetic sequence that belongs to the virus, rendering it harmless. Without clear instructions, bacteria cannot become a factory for new viruses and are not in danger of ending badly.
Edition
Cas9 is an extremely precise protein for cutting pieces of DNA. When Chapentier and Doudna saw this in the course of their studies, pooling knowledge gathered separately from years of research and with other researchers, they wondered if they could leverage Cas9 to program the CRISPR system and use it to edit genetic material. The rather ambitious goal did not deter them and led to the creation of a “genetic scissors” system described in their study published in 2012.
Simplifying a lot, the CRISPR / Cas9 scissors to modify the genetic material in a cell work from a genetic sequence (guide RNA) elaborated by researchers that corresponds to that of the DNA where the cut must be made in the cell. The Cas9 protein goes to work and makes the cut: If there are no other instructions, cells repair their DNA by losing a part of their genetic code, resulting in the loss of instructions for the gene that the researchers wanted to turn off. The system also allows new DNA to be grafted in the repair stage, in case researchers want to further modify the cell’s function.
(Nobelprize.org)
Opportunities and dangers
Before the advent of CRISPR / Cas9, editing genes in a cell was extremely difficult, time-consuming, and often produced unreliable results. Thanks to genetic scissors, on the other hand, changes can be made much more precisely and quickly. The system is now widespread in many fields of research, although it is not always easy to master and has shown that it needs some improvement.
In recent years, researchers have used CRISPR / Cas9 primarily to better understand how genes work and their interactions, for example in the case of diseases in some animals. The technique is also used to modify the genome of plants, in order to make them more resistant to drought, or to particular parasites, reducing the need to use chemical compounds that are potentially harmful to our health.
CRISPR / Cas9 is also considered a very promising resource to develop new treatments against some inherited diseases, even if the results obtained remain partial and the techniques to be refined. Researchers are also experimenting with the use of CRISPR to modify our immune cells, making them capable of searching for cancer cells more effectively.
Such a precise genome modification system also opens up still unexplored and ethically controversial scenarios. In theory, CRISPR / Cas9 could be used to create genetically modified humans. It could offer enormous benefits in reducing the risk of births with serious inherited diseases, but it could also lead to irreversible changes in our genetic makeup, passed down from generation to generation. We are still very far from these eventualities, but for that very reason many invite us not to underestimate a central debate and in a certain existential sense.
Emmanuelle Charpentier was born in 1968 in Jubisy-sur-Orge in France and is director of the Division of Pathogen Sciences of the Max Planck Institute in Berlin, Germany.
Jennifer A. Doudna He was born in 1964 in Washington, DC (United States) and is a professor at the University of California, Berkeley.
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