This year’s Nobel Prize in chemistry went to the ground-breaking gene editing method known as CRISPR/Cas9, developed by Emmanuelle Charpentier and Jennifer A. Doudna.

This gene editing system has revolutionized the biological sciences: With this tool, researchers are able to add, replace or remove pieces of the genetic makeup of living beings, which has had tremendous impacts on our understanding of gene function and disease, paving the way towards the development of new therapies.

Many diseases are caused by genetic mutations, that is, changes in the normal DNA sequence. For that reason, the idea of changing a person’s DNA to treat illnesses is very enticing and now closer to reality than ever before.

But how was this tool discovered?

 The CRISPR/Cas9 tool is an adaptation of an ancient defense system that bacteria use to fight viral infections. The genetic material of bacteria contains a region called CRISPR (clustered regularly interspaced short palindromic repeats), which is composed of repetitive DNA sequences that are interspaced by unique sections. These spacers are short fragments of viral DNA that bacteria incorporate into their own genome as a reminder of the infection, much like a mugshot of a criminal. The CRISPR DNA is then copied into a molecule that is able to recognize the viral DNA in case of re-infection. In addition to the CRISPR sequences, bacteria also contain CRISPR-associated (Cas) genes that code for scissor-like proteins. This way if the bacteria becomes reinfected with the same virus, its genome will recognize it and the scissor-like proteins will be able to cut the virus’ DNA, destroying it.

CRISPR/Cas9  is a defense system that bacteria use to destroy DNA from viruses. It can be adapted to ‘edit’ or ‘delete’ any part of the human genome to treat diseases

How exactly does the engineered CRISPR/Cas9 system work?

After the astonishing discoveries regarding this bacterial defense mechanism, researchers found that they could adapt this system to edit any desired DNA sequence, by simply designing a molecule to match the target site. After introducing the system into the cells, the CRISPR/Cas9 complex scans the genome to find the specific region to be changed, which matches the target molecule made in the lab. Once the match is found, the Cas9 protein cuts the DNA!  This could introduce the “healthy version” of a gene or repair the existing one.

This programmable and extremely precise gene editing tool has allowed researchers to easily change the genetic code of cells and animals for basic research. In this way, if scientists want to unravel the function of a specific gene, they can now disrupt that DNA region using the CRISPR/Cas9 system and observe the effects that it has on the cells. This system also allows the deletion of certain genes to create models of disease which can then be used to better understand the pathology and to explore potential treatments.

Genetic engineeering concept with 3d rendering dna helix and a part of dna
The CRIPR/Cas9 system is currently in clinical trials for the treatment of cancer and inherited diseases

Not surprisingly, one of the most promising and explored uses for CRISPR/Cas9 is the treatment of human diseases. New cancer therapies are already being investigated in clinical trials and, more recently, researchers have started looking into ways of curing inherited diseases, such as sickle cell disease and blindness.

Nevertheless, this amazing discovery also raises a lot of ethical questions. One of the most controversial topics around CRISPR/Cas9 involves its use to modify embryos, which is currently prohibited. Altering the DNA from egg and sperm cells sounds particularly convenient, since it would treat the root of many problems, allowing disease-causing alterations to completely disappear from an individual’s lineage. However, this technology still lacks the specificity, predictability and safety needed to be used in this way. The human genome has an extremely complex nature, containing millions of genes that sometimes perform several functions, most of which are still unknown. Consequently, although editing a gene might solve a problem, it might also lead to other unwanted and unexpected effects. Moreover, technology developments need to assure that only the desired gene is changed, without any off-target cuts.

Overall, the rapidly growing knowledge around these “genetic scissors” is highly promising and will most likely result in safety improvements, providing hope for the cure of many diseases in the near future.