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New gene technique inspired by bacteria´s immune defence

Photo: Shutterstock
Photo: Shutterstock

Variations and changes in the genetic code in our cells are of great significance for many of the most widespread diseases. In recent years, researchers have made important progress in finding new ways to correct the genes that are causing problems. They have developed a technique that enables changes to the genetic sequence in living cells.

 “It is possible to cut out the bad genes and paste in new, healthy genes”, explains Johan Jakobsson, researcher in molecular neurogenetics at Lund University.


This has led to the technique often being referred to as the “gene scissors”. The scientific name for it is CRISPR/Cas9; the technique is inspired by the way in which bacteria protect themselves from viral attack by cutting up the virus’s DNA and pasting bits of it into their own genome – as a kind of immune defence.

Help us cure many serious diseases

Johan Jakobsson is working on developing the method and seeing how, in the future, it could help us to cure many of today’s serious diseases such as Alzheimer’s, Parkinson’s, Diabetes and some blood disorders. He heads the Molecular Neurogenetics Lab in Lund, where he is trying to build up a technical platform that can help researchers in these fields.
CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats” – which may sound very long and complicated but describes a type of gene sequence that is present in the genome of bacteria. The sequence features genes for a certain type of proteins that can divide and split DNA. There are also repetitive sequences that do not code for proteins, and between them are short, unique genes originating from viruses that the bacteria have encountered. The system functions as the bacterium’s immune defence system and helps it to recognise and neutralise foreign DNA.


Usually, when a bacterium is attacked by a virus, the virus can hack it by injecting its DNA into the bacterial cells, making it produce more viruses for example. But if the bacterium has encountered that virus previously, its defence mechanism is activated and destroys the virus. Once the bacterium has neutralised a virus, it can paste the DNA parts from the virus into its own DNA and increase its defence. The CRISPR/Cas9 technique functions in a similar way.


“One can cut and paste in the gene sequences” says Johan Jakobsson, continuing:
“If you could repair or replace genes in people who are already ill or those with a high risk of developing a disease, you would be one step closer to a cure”.

The puzzle piece that takes gene therapy to the next level

CRISPR/Cas9 could become an important addition to the genetic toolkit that researchers have at their disposal when looking for new treatment methods to cure serious diseases. It could be applied, for example, in various forms of gene therapy that involve introducing one or several new genes into the cells that cause the diseases. If you can create stem cells in which defective genes are corrected and introduce them into the body, you might hopefully cure many serious diseases. Stem cells are cells that can give rise to many different types of cells and tissues.


“I am convinced that CRISPR will become extremely important in the future”, says Johan Jakobsson, explaining that the method could be the puzzle piece that takes gene therapy to the next level.


Unfortunately, that could take time. Johan Jakobsson wants to emphasise that this is a long-term goal and that there is a long way to go before it will be possible to use this method clinically. However, the method works well in cell cultures and has also been used in simple animal experiments.

 

“It is relatively easy to cut and paste in DNA”, says Johan Jakobsson, but he explains that it is not equally easy to make specific changes in genes – for example to replace individual bases in the sequence, such as replacing an A with a G.

 

In the lab, Johan Jakobsson also uses the gene scissors to try to make changes in the genome in brain stem cells, in order to see how that affects the brain and its development. The aim is to find out which genes and genetic changes are significant to neurodegenerative diseases, such as Alzheimer’s, as well as psychiatric diagnoses such as schizophrenia and autism.