What is genome editing and how does it work?

New scientific techniques are constantly being developed, and some have the potential to make a large impact on future research and have possible applications for health. One technique showing great promise is CRISPR-Cas9, which can be used as a genome-editing tool.

As with any scientific advance, it is important that society has sufficient understanding of the potential of these techniques to make informed decisions about how and when they should (and in some cases, should not) be used. Hannah Isom and Kate Arkless Gray have collected answers to some common questions about CRISPR-Cas9 and genome editing.

What is CRISPR-Cas9?

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, enabling 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.

So how does it work?

We've actually borrowed the technique – or at least the principle – from nature. Some bacteria use a similar in-built gene editing mechanism to protect themselves from harmful viruses – a sort of rudimentary immune system.

It 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.

When the cut is made the DNA starts to repair itself, but because this natural repair method is error-prone 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 a desired DNA sequence to replace what was originally there, though this requires a slightly more complicated process.

Is this the first time we've been able to edit the genome?

No. Scientists have been able to make changes to the DNA in cells for a while and have used these techniques widely in research. But, CRISPR-Cas9 is widely acknowledged to be a game-changer because of the speed, simplicity and specificity with which edits can be carried out. It even allows researchers to make more than one edit at a time.

Due to its relative simplicity, the potential applications of CRISPR-Cas9 have become a hot topic of discussion, particularly the idea that it may one day be used to make edits to human reproductive cells or embryos (known as the germ line), that could then be passed to future generations.

Why would you want to edit genetic code in the first place?

There are lots of reasons scientists are interested in this idea, for starters it can be used as a powerful research tool. By making changes to genes using CRISPR-Cas9 and studying the effects, we 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.

This type of pre-clinical research may involve studying cells or tissues in a petri dish – which may include very early human embryos, under very strict conditions (it is illegal to implant these to create a pregnancy).  It's also possible to use CRISPR-Cas9 to introduce or remove genes in research animals (such as fruit flies, mice, zebrafish) so we can study the effects in living organisms.

Understanding more about diseases processes in this way can help in the development of new treatments.

So, it's useful for research. What about treatments?

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 such approach 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 thalasaemia.

Another interesting avenue of research is in CAR-T cell therapy for cancer.  Here researchers are looking at using CRISPR-Cas9 to make changes to immune cells so that they can recognise and target tumours.

However, it is likely to be many years before any of these techniques are being used routinely in patients.

Can we edit human embryos?

CRISPR-Cas9 and other genome editing techniques have sparked a lot of interest, and some people believe that we should also explore the possibility of using them to prevent children being born with serious inherited diseases. One question is whether this could be done by editing the genome of embryos during the IVF process.

In reality, we currently know far too little about the technique to be able to use it in this way and even if our technical understanding had reached this stage, it is illegal in the UK and many other countries to edit the genome of an embryo and implant it into a woman to create a pregnancy. In fact, any research that involves human embryos is governed by strict legal, ethical and scientific regulations.

Even so, we believe it is important to start an open conversation about potential applications now, so that the ethical, safety, and legal issues can be widely debated. We need to consider a wide range of voices and opinions (not just those of scientists) to inform any future decisions.

Is this a slippery slope towards designer babies?

When discussing genetic research and how it may be used to improve health in future, we often hear the phrase 'slippery slope', which can cause alarm. The law currently forbids any use of this technique in human reproduction.

Some people are concerned that in future CRISPR-Cas9 could be used to engineer 'desirable' traits into babies, such as appearance, physical prowess or intelligence. These are complex traits, affected by both nature and nurture. We are a long way from being able to engineer these things and society may choose never to allow this. Editing any traits that can be inherited – even for health reasons – is a big step for humanity and so there needs to be a wide ranging discussion before we consider whether to allow this.

We wholeheartedly support the UK's robust regulatory framework, which ensures that science progresses at a rate that society is comfortable with, and potential uses of technology such as genome editing undergo a high degree of scrutiny before being permitted.

Changes to the law should only ever be considered after extensive public consultation, ethical and scientific review. We must consider all concerns and ethical implications of being able to manipulate the genome before we consider making any changes to current rules and regulations.

In every case so far, this has meant that procedures have only ever been approved when they have shown compelling medical reasons to justify their use (as in the case of IVF and mitochondrial donation).

How is Wellcome involved?

The Wellcome Trust has funded a number of scientists who use CRISPR-Cas9 in their research. These include a collaboration between AstraZeneca and the Sanger Institute, who are working to use genome-editing technologies to identify and validate new drug targets for cancer, heart disease and diabetes.

Last week, we published an initial joint policy position [PDF 87KB] with several other research bodies, reinforcing our support for further research in this area, which we believe holds a great deal of promise.

We are not currently funding any genome editing research that involves human embryos, but would be open to doing so in the context of thorough ethical scrutiny and approval, high-quality science, and in accordance with all legal and regulatory requirements.

If the clinical applications are years away, why are we talking about this now?

We think it’s important to have an open and inclusive debate sooner rather than later so that scientists, ethicists, doctors, regulators, funders and policy makers can exchange knowledge and ideas on the issues and also to encourage the public, including patients and their families, to feed into those discussions.

There are lots of activities already in progress, including a project by the Nuffield Council on Bioethics looking at the impact of genome editing, a meeting of international experts called the Hinxton Group and an initiative led by the US National Academies of Sciences and Medicine.