What is CRISPR-Cas9?

CRISPR-Cas9 is a technology that can be used to edit parts of the genome of organisms. This can be done by either adding, removing or altering parts of the genome. At the current moment in time, CRISPR-Cas9 is the simplest and most precise method of editing the genome that is available. It is cheaper and faster than all previous methods of editing DNA, and it also has a higher precision. CRISPR stands for clustered regularly interspaced short palindromic repeats. Cas9 is the name of a protein that is relied upon by the CRISPR system of a species of bacteria called Streptococcus pyogenes.

This system is a simpler CRISPR system, and can and has been used to edit the genomes of a wide range of different organisms, including fruit flies, plants, and even human embryos. CRISPR-Cas9 consists of segments of DNA that are made up of short repetitions of DNA separated by short segments of spacer DNA, which is non-coding DNA. Non-coding DNA is DNA that does not code for anything, which means that it does not produce any protein, and therefore it has no effect.

How does it work?

There are two key parts of CRISPR-Cas9, which work together to create a change in the DNA, known as a mutation. There is the Cas9 enzyme, which cuts the DNA in a particular place. This then allows the addition or removal of bits of DNA. The other key part is a piece of RNA which is known as guide RNA or gRNA. This guide RNA guides the Cas9 enzyme to the right part of the genome so it can cut the DNA in the correct place.

The guide RNA is specially designed to be able to find the correct part of the genome. It is complementary to the target DNA, which means that it is the opposite of the target DNA, and will therefore bind to it. Because this process is very specific, the guide RNA will bind only to the target DNA, and not to any other sections of DNA in the genome.

When the guide RNA binds to the correct DNA sequence, the Cas9 enzyme follows it and will cut the DNA. This leads to the cell which contains the DNA recognising that the DNA has been damaged, which leads to the cell attempting to repair the DNA. This process of repairing DNA can be utilised to change the DNA as it is being repaired. This can involve adding and removing bits of DNA.

Uses of CRISPR-Cas9

One important use of CRISPR-Cas9 is to treat diseases that have a genetic component. This includes diseases that are genetically inherited, such as Huntingdon’s disease, but also diseases that have genetically inherited risk factors. These are genes that make a person more susceptible to suffering from a particular disease. Many diseases have been shown to have genetic risk factors which make people more susceptible to that disease, and therefore more likely to suffer from it. There is great potential to use CRISPR-Cas9 to edit the genome of embryos that carry genes that cause disease or susceptibility to disease. This would mean that the embryo would develop into a child that does not have that gene, and would therefore not suffer from the disease or would not be susceptible to the disease.

Another use of CRISPR-Cas9 is in biomedicine. It can be used to target DNA sequences that are of medical interest. DNA sequences of medical interest include genes that cause undesirable traits in pathogens, such as antibiotic resistance. These genes can be removed using CRISPR-Cas9, which makes it much easier to fight the pathogen and treat the illness. There is also research that shows that CRISPR-Cas9 can be used to limit the replication of herpesviruses. Herpesviruses are a group of different viruses that cause recurring infections. In one herpesvirus, called Epstein-Barr virus, CRISPR-Cas9 has been shown to be able to completely eradicate all viral DNA. This is very useful as Epstein-Bar virus can cause cancer, so eradicating it is a priority.

Another use of CRISPR-Cas9 is in organ transplants. Currently, animal organs can not be transplanted into humans. This is because of retroviruses, which are a type of virus that produce DNA that is incorporated into the infected cells. There are retroviruses present in the genomes of other animal species which can be harmful to humans. These retroviruses would be harmful to transplant patients if animal organs were used for the transplant. However, there is the possibility of using CRISPR-Cas9 to remove retroviruses from animal genomes. This would stop organ transplants from animals being harmful, and allow them to be used. This would of course be highly significant, considering the considerable lack of organs available for transplant patients, and the long waiting times for transplanted organs. Allowing the use of animal organs in transplants could save many lives.

Legality and ethics

There are many plans to conduct further research on the potential to use CRISPR-Cas9 for applications editing the human genome. However, many scientists have expressed a desire for there to be a worldwide moratorium on using CRISPR-Cas9 to edit the human germline – egg and sperm cells. Editing the human germline would result in people whose cells all contained edited DNA.

It has been suggested that the full implication of such applications must be fully discussed by governments and scientific organisations. The International Summit on Human Gene Editing in 2015 discussed the use of CRISPR-Cas9 for editing human germlines, and they agreed to support basic and clinical research. They also made a specific distinction between editing germline cells and somatic cells, which are all cells other than sex cells and stem cells. This is because changes to the genomes of germline cells can be inherited by future generations, whereas changes to somatic cells can not.