Edit genes like it’s a video game, this is how the new CRISPR tool works

Can you imagine being able to cut and copy part of a DNA sequence to get the mixture that interests us the most? Well, this is what seems more typical of a video game graphics engine, achieved by a group of scientists working on the CRISPR genetic editor.

Today we will talk about new technique which improves the gene editing toolbox CRISPR. The system, known as PASTE, uses viral enzymes to drag large sections of DNA into the genome, which could help treat a number of genetic diseases.

The CRISPR system originated in bacteria, who use it as a defense mechanism against the viruses chasing them. Basically, if a bacterium survived a viral infection, it used CRISPR enzymes to cut out a small segment of the virus’s DNA and use it to remember how to fight future infections with that virus.

In recent decades, scientists have adapted this system to make it a powerful genetic engineering tool. The CRISPR system consists of an enzyme commonly referred to as Cas9, which cuts the DNA, and a short RNA sequence that directs the system to make that cut in the correct section of the genome.

This can be used to remove problematic genes, such as those that cause disease, and replace them with more beneficial ones. The problem is that this process involves breaking two strands of DNA, which can make it difficult for the cell to repair them properly, leading to unwanted changes (and the risk of cancer).

Advanced tool that protects the patient

Therefore, researchers at the Massachusetts Institute of Technology began to develop a new version of the tool, which will be more gentle on the genome. Instead of the cut and paste method of the current CRISPR-Cas9, the command describes a new method in the form of a “drag and drop” system.

PASTE, which stands for Programmable Addition Through Site-Specific Target Elements, still uses the Cas9 enzyme to cut the DNA at the site indicated by the guide RNA, but the difference is that the new system cuts one thread and then another instead of both.

The insertion of new genes is carried out by enzymes called serine integrases, which are used by viruses to infect bacteria and insert their DNA into the target’s genome – an irony, given the origin of CRISPR as protecting bacteria from these same attacks.

These integrases naturally look for specific sequences in the target genome, so after the PASTE system makes its smooth cut, it will insert the small “landing site” sequence that integrases are looking for. Finally, integrase inserts its DNA payload into the genome at this location.

This method has success rate was up to 60% and caused very few errors at the insertion point. However, tests on mice with “humanized” livers only worked on 2.5% of the cells.

This CRISPR method is not only gentler and potentially safer, but the team claims it was able to insert a huge amount of DNA at once – up to 36,000 base pairs in tests. The researchers explain that this could make it particularly useful for replacing defective genes, such as those that cause cystic fibrosis.