The Crispr / Cas9 gene scissors are one of the most important tools in modern genetic engineering and biomedicine. That is why the 2020 Nobel Prize in Chemistry goes to the two researchers who discovered the gene scissors and developed them for practical use: Emmanuelle Charpentier and Jennifer Doudna. They were the first to recognize that a bacterial-generated construct from a segment of DNA – Crispr – and an enzyme – Cas9 – can be turned into a genetic engineering tool. Because Crispr / Cas9 can cut the hereditary molecule DNA with pinpoint accuracy and exchange gene parts.
The Crispr / Cas9 gene scissors have become an indispensable part of modern biomedicine and genetics. For the first time, it makes it possible to precisely and relatively easily cut out individual sections or even just individual bases from hereditary molecules and replace them with other DNA sequences. The gene scissors are accurate, cheap and so easy to use that even genetic engineering laypeople can quickly get the hang of it. A few years ago researchers compared the importance of this method with that of Volkswagen for the automotive industry – it has become a common technology.
Two researchers make the breakthrough
This milestone in genetic engineering was made possible primarily by the work of Emmanuelle Charpentier from the Max Planck Research Center for the Science of Pathogens in Berlin and Jennifer Doudna from the University of California at Berkeley. They were the first to develop a functional version of the gene scissors that can be adapted to the desired DNA sequence. Her research is based on an immune mechanism discovered in bacteria: to defend themselves against invading viruses, the microbes use a certain part of their genetic make-up, the “Clustered Regularly Interspaced Short Palindromic Repeats” – Crispr for short – to recognize and identify viral DNA sequences then cut up with enzymes. However, it was initially not possible to activate the Crispr isolated from bacteria in the laboratory.
The breakthrough came with Charpentier’s knowledge in 2011 that apparently another molecule, the so-called tracrRNA, was necessary for recognizing and cutting the foreign DNA. Together, Charpentier and Doudna then developed a version of the gene scissors in which the tracRNA is already integrated. Using this “guide RNA”, your construct now made it possible to specify specific DNA segments as “targets”. This is possible because the code of the guide RNA from Crispr / Cas9 contains a kind of negative of the gene segment being sought. Where this negative matches the gene code of the DNA to be edited, the gene scissors attach themselves and the Cas9 enzyme cuts out the piece. In laboratory tests, Charpentier and Doudna tested their development with five different objectives – and in all tests the genetic scissors cut exactly where they should. In 2012, the microbiologists published their results – and triggered a revolution in genetic research.
“An enormous power that will affect us all”
In the meantime, Crispr / Cas9 has become one of the most important tools in gene editing. It is used in medical research to switch off specific genes in laboratory animals or to add genetic defects that occur in humans to their genome. This is crucial, for example, to be able to research certain hereditary diseases. The genetic scissors are also used to modify the genetic makeup of crops so that they can better tolerate heavy metals, heat or drought, for example. In medicine, the gene scissors open up new possibilities for gene therapies against hereditary diseases or immunotherapies against cancer. In mice it has already been possible to destroy the HIV virus in cells, to cure Duchenne’s hereditary muscle weakness or to repair the genetic defect of sickle cell anemia. “This genetic tool has tremendous power that will affect us all,” said Claes Gustafsson, chairman of the Nobel Committee on Chemistry at the award ceremony. “The gene scissors not only revolutionized basic research, but also created innovative crops and will lead to groundbreaking medical treatments.”
However: the gene scissors are very precise, but not flawless. Therefore, in some cases it can also cause undesirable and potentially harmful DNA changes. In addition, the introduction of new genes can cause undetected long-term effects. This is one of the reasons why this tool has so far mainly been tested on animals and plants. But some research groups, especially in China, are also experimenting with the use on humans – in some cases in an ethically questionable manner. In 2018, for example, two children were born for the first time in whose genetic material scientists had smuggled a defense gene against HIV. Since they have already introduced this gene into the fertilized egg cell, all cells of the two girls carry this gene change – including the egg cells they later produce. This represents an intervention in the germline – something that has so far been banned in most countries because of its far-reaching consequences and ethical consequences.
Source: nobelprize.org