Most genetic conditions have no cure, where treatment is available this is more often than not with the intention of managing symptoms or slowing deterioration rather than stopping the disease altogether. New scientific techniques are constantly being developed, and some of them have the potential to make a large impact on future research and have possible applications for health. Genome editing technologies, such as CRISPR-Cas9, present a promising way of addressing the cause not just the symptoms of genetic conditions.
CRISPR-Cas9 is a new technique that allows scientists to edit the genome by removing, replacing, or adding to parts of the DNA sequence. It’s not the first tool to allow us to do this, but it is by far the most efficient, inexpensive and easiest to use. CRISPR-Cas9 allows for precise genetic manipulation in practically any living cell, even those inside the body. If you think of the genome as a book filled with millions of letters of genetic code, CRISPR-Cas9 can be used to insert or delete new words (genes) or even make a change to a single letter.
CRISPR-Cas9 uses a pair of ‘molecular scissors’ that cut the two strands of DNA at a precise location so that bits can be added or removed. These molecular scissors are actually an enzyme called Cas9, which is attached to a small piece of RNA (a close cousin of DNA) that helps guide the scissors to the desired location.
Once the cut is made, the DNA starts to repair itself. However, this natural repair method is error-prone, and it can cause bits of DNA to be added or deleted. When this happens, it can change the way the gene at that location works.
In some circumstances, it is even possible to insert the correct DNA sequence to replace what was originally there though this requires a slightly more complicated process.
There are lots of reasons scientists are interested in this technology, starting with the fact that it can be used as a powerful research tool. By making changes to genes using CRISPR-Cas9 and studying the effects, researchers can learn more about what these genes do in the body and how they might be involved in causing disease. It is particularly useful for studying diseases that involve more than one gene, as it can be used to edit the genome in several places at once. Understanding more about diseases’ processes in this way can help in the development of new treatments.
In the short term, the most likely application is to understand better human biology. In the longer term, researchers may be able to develop clinical applications.
It is hoped that genome editing could have many different applications for patients in the future. CRISPR-Cas9 has a lot of potential as a tool for treating a range of medical conditions that have a genetic component. CRISPR-Cas9 has shown a lot of promise as a potential treatment in human somatic (non-reproductive) cells. Several teams around the world are already using CRISPR-Cas9 and other genome-editing techniques to develop therapies for a range of conditions.
One example is a type of gene therapy where cells are taken from the body and their DNA rewritten to correct a fault, or add a new function, before being put back into the patient. There is already work underway to apply this principle to bone marrow cells as a potential treatment for sickle cell disease and another blood disorder called thalassaemia.
The first licence granted in the UK allowing a research team to alter genetically human embryos using the CRISPR-Cas9 method was issued in January 2016. Researchers at the Francis Crick Institute proposed to modify genes to explore why some women have repeated miscarriages. This could potentially lead to breakthroughs in clinical medicine, but it has been indicated that their data would be used to enhance conventional techniques in IVF, not to begin editing genes for reproductive purposes.
One of the significant objections about the use of genome modification is regarding the safety of using this type of technology to produce human life. While the CRISPR-Cas9 technique is much more reliable than its predecessors, this does not mean that it is reliable enough to start using in human reproduction.
Because any changes made in germline cells – the eggs or sperm – including potential mistakes, will be passed on from generation to generation, it has important ethical implications.
CRISPR-Cas9, as with many new biological techniques, carries potential risks and as yet we do not know the long-term impact of using the technique. Concerns about the safety and accuracy of the method at this stage are valid. Concerns of this nature are one of the reasons why carrying out gene editing in germline cells is currently illegal in the UK and most other countries. Steps to use the technology on humans would not be allowed until it is definitely safe for future generations as well as the individuals being treated.
The fact that changes would pass between generations could, however, be seen as one of the most exciting implications of the technique. The fact that changes will carry down generations could mean the eradication of life-limiting and fatal genetic conditions from families that have been affected for generations.