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A method of gene editing was accidentally improved, for which the Nobel Prize was awarded in 2020

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CRISPR/Cas9 is one of the most popular gene editing techniques. Its creators were awarded the Nobel Prize. Now – by chance – a group of scientists from one of the American universities found a way to make the method even more efficient.

Scientists improved the famous CRISPR/Cas9 gene editing method, increasing its efficiency several times. At the same time, they detected a previously unknown way of repairing genes in cells.

Cross connections

Since its development, the CRISPR/Cas9 gene manipulation method has become a permanent fixture in biotechnological laboratories around the world. In 2020, she even received the Nobel Prize. It uses natural methods used by bacteria to fight viruses.

The bacterium detects viral DNA and adds it to its genetic material so that it can quickly detect and destroy such DNA in the future. Biotechnologists use enzymes acting in this mechanism and natural mechanisms that repair cellular DNA to incorporate selected DNA into the genome of a cell, for example a human one, as part of gene therapy.

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Scientists from the US University of California in Santa Barbara have managed to improve the incorporation of new genes into the cell genome several times. In the inserted DNA, they formed so-called cross-links, connecting different sections of the double helix to each other.

Nobel Prize in Chemistry 2020Maciej Zielinski/PAP

“We damaged them”

Such DNA is inactive because the cell treats it as defective. However, as it turned out, in contact with it, cells launched powerful, previously unknown repair processes and incorporated this DNA into their genome.

“Basically what we did was take the DNA and damage it,” said Chris Richardson, co-author of the paper published in the science journal Nature Biotechnology. We damaged them in the worst way imaginable. But the cell phone didn’t say, “Hey, this is garbage and I’m going to throw it away.” She said, “Hey, that looks great, I’ll paste it into my genome,” the biotechnologist explained.

This discovery was a happy coincidence. While working on protein purification to study DNA repair mechanisms, lead author Hannah Ghasemi noticed unexpected changes in the results of her experiments.

– We made chemical modifications to the DNA to be able to extract it from cells and see which proteins attach to it. I was just checking whether such a modification affected the editing of these genes in any way – she said. “I expected either no changes or that the edition would be weakened,” she added.

Instead, it turned out that the cross-linked DNA was edited three times more intensively than normal DNA in the cell. Moreover, despite more intensive editing (which means a greater risk of errors), the researchers did not find an increase in the number of mutations.

DNA – illustrative photoShutterstock

They already know where to use it

Now, scientists are looking at various mechanisms that could have led to the observed results. “We think the cell is detecting and trying to repair damaged DNA to which we have added unusual connections,” said Richardson.

According to the scientists, the new method will rather be used for ex-vivo gene manipulation, i.e. for laboratory research, for example on diseases. ‘We can now switch off different genes more efficiently and insert new segments into genomes to conduct research outside the human body, in the laboratory,’ explained Ghasemi.

Main photo source: Shutterstock

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