Vocabulary and FAQs

Genomics is the study of all of a person’s genes and how they work together in the body.

Therapeutic Genomics is a new approach that uses what we learn from genomics to discover new treatments for diseases.

Nearly every cell in your body contains DNA, which is a blueprint for how to build the body.  There is some natural variability in DNA (which is why we don’t all look and act the same), but sometimes changes in DNA can cause problems or diseases.

Genetic Medicine aims to help patients by either:

• changing the DNA itself, or
• interrupting, blocking or changing the instructions that the DNA is giving the cell.

Currently, Genetic Medicine usually focuses on one disease at a time -- for example, working on a cure for Huntington’s, or Cystic Fibrosis, or Duchenne Muscular Dystrophy.

Our goal is to use Therapeutic Genomics to change how therapies are developed. We want to find out the best way to treat any disease by reusing different tools from the same toolkit.  

To make this more manageable, we are focusing on Genetic Rare Disease -- diseases caused by a “typo” in a single gene.  We will begin with a few example diseases in the blood, eye and brain, and then use what we learn to help other diseases.

Along with creating new genetic therapies like ASOs, oligos and gene editors, and finding ways to deliver them to the right cells, we are also building AI models and decision-support tools to help with questions like: 

• Can this person's condition be treated with our current tools?
• Which combination of tools might work best?
• Which unwanted effects we should be especially careful to avoid?

Our partners at the University of Berkeley Innovative Genomics Institute created a fantastic resource for this. 

The CRISPR Made Simple website is designed kids or anyone starting from scratch, with a guide to the basics of DNA, genes, and gene editing.  https://innovativegenomics.org/crispr-made-simple/.

We have the potential to revolutionise healthcare by bringing therapies to thousands of rare genetic disorders, and gene- and cell-specific therapies to common disorders. 

We have seen that it is possible to create genetic medicines (e.g. for sickle cell disease in 2023), to create bespoke genetic medicines for a single patient, and as of May 2025 members of the MRC CoRE TG team demonstrated that individualised gene-editing therapy can be created and delivered in only a few months.

However, these examples are currently rare, and each of them required tremendous effort from teams of hundreds of people.  Over the next 7-14 years (up to 2038), we want to take these lessons, and turn them into a toolkit which can be more easily shared and used.

We believe it should be possible for (at least some) patients to go from diagnosis to therapy in 100 days, but this will require many things to change.  

We need to advance the science, but also the way these therapies are regulated, how quickly and cheaply personalised medicines can be manufactured, and whether healthcare systems and insurers are equipped to actually deliver them.

The MRC CoRE is seeking to build a flexible toolkit, so this list will grow and change over time.  Our current tools include:

• ASOs and Oligos (Antisense Oligonucleotides and Oligonucleotides)
• CRISPR
• Endosomal Escape Vehicle (EEVs)
• Lentiviruses
• Lipid Nanoparticles (LNPs)

No. 

Gene therapies are carefully targeted.  We try to send them only to the cells that need help.

There are several reasons for this.

First, there is no reason to change healthy cells. For example, if a disease affects the brain, treating muscle cells would not help. Also, the same gene can have different jobs in different kinds of cells. A gene that causes problems in one place might be helpful in another.

Second, we want to give the smallest dose possible. Smaller doses are safer and lower the chance that the immune system will react badly.

Your body has many natural defenses that protect cells from foreign DNA or instructions. Different types of cells have different defenses. Some defenses are part of the cell itself, like special proteins on the cell surface. Others are body-wide protections, like the blood-brain barrier, inflammation, scar tissue, or immune cells that attack the treatment. Gene therapies must be designed to get past the defenses of the specific cells we want to treat.

The immune system and the liver are very good at catching and removing medicines before they reach their target. To avoid this, doctors often deliver the treatment directly where it is needed. For example, medicine can be injected straight into the eye for eye diseases. For some blood diseases, doctors take blood out of the body, treat the cells, and then put them back. For the Huntington's disease therapy in September 2025, patients had an 8-hour brain surgery so the treatment could be delivered to the right part of the brain.

Because of all this, gene-editing therapies do not change sperm or egg cells. Any changes made to a patient’s cells cannot be passed on to their children.

Finally, ASO or oligo therapies do not change a person’s DNA at all. They work for a while and then wear off over time.

We need to understand where the problem is happening in the body.

• Which cells are affected?  Do we know how deliver a treatment to those kinds of cells?

We need to understand what the treatment needs to do.

• Does the patient have one healthy copy of a gene and one faulty copy? Or are both copies faulty?
• How many healthy copies are needed for the treatment to work?

Sometimes, we don’t need to change the DNA itself. 

We may only need to change how the gene’s instructions are used.

• Do we need to turn a gene up, turn it down, or turn it off completely?
• Do we need to do just one of these things, or more than one at the same time?
  For example, we might need to turn off a harmful gene while also turning up a helpful one.

In other cases, we do need to change the DNA.

• Is the problem caused because something important is missing, so we need to add new instructions?
  Or is it caused by harmful instructions, so we need to remove or fix them?
• Do we need to change a whole gene (gene augmentation or gene replacement), or just fix one or two “letters” in the DNA (base editing)?

We also think about how long the treatment needs to work.

• Do we need to make a permanent change to the cells?
  Or is it enough to change their instructions for a short time, such as while an organ is growing or healing?

Finally, we check whether the treatment can actually be delivered.

• Will the genetic instructions we need fit inside the delivery tool we are using to carry the therapy into the target cells?

The MRC CoRE is working to create decision-support tools to help guide researchers to answer these questions for each patient and each new potential therapy.

First, we need to know how long the treatment needs to work.

• Does the change need to last forever?
• Or does it only need to help for a short time, such as while an organ is growing or healing?

Then, we need to consider the available technology.

• Can we use tools that already exist?
• Or do we need to invent new tools to make the treatment work?

We also need to think carefully about how to deliver the treatment.

• What is the safest way to get the treatment into the right type of cells?
• Can that delivery method carry the right amount of genetic instructions?

Another important question is dosing.

• Is it safer to give the treatment once?
• Or is it better to give smaller doses over time?

Finally, we must think about practical challenges.

• Does the treatment need to be given in a special hospital or by highly trained doctors?
• Will the patient need extra care or monitoring while they recover?

The MRC CoRE is working to create decision-support tools to help guide researchers to answer these questions for each patient and each new potential therapy.

First, we look at what we already know about the tools we want to use.

• What are the strengths and weaknesses of the delivery system?
  How well do we understand the technology that targets the right cells and carries the genetic instructions?

Next, we think carefully about the gene itself.

• Does this gene do other important jobs elsewhere in the body?
• Could changing it cause problems we didn’t expect?

What can we predict about off-target effects?

Even though gene editing tools can be very precise, the process is not perfect. Each treatment molecule moves on its own and we cannot guarantee that it will reach the exact right cell or spot in the DNA every time.  Sometimes, the editor can land in the wrong place in the DNA if it looks similar to the target. This is called an “off-target” effect, and it could cause unwanted changes.

We ask several questions about this.

• Can we predict where these off-target changes might happen?
• What problems could those changes cause?
• Can we design the treatment to lower the chance of this happening?

To help with this, the MRC CoRE is building computer models and AI tools to predict what might happen if the wrong part of DNA is changed. They also work with regulators to develop tests that can help avoid or reduce known risks.

Before giving treatments to patients, we need to do as much testing as possible in the lab. We need to use:

• Screening tests, where we try treatments on specially made cells or animal models.
• Computer simulations to make predictions.
• Experiments to check whether the computer's predictions are correct.

The MRC CoRE is working to improve the kinds of tests and computer models that are available, and to understand which tests give the most trustworthy results.

Even with all this testing, gene therapies are very personal, and no test can catch everything.

So we also ask:

• What risks might still be unknown?
• Where are the gaps in our testing, and what are the things we know we don’t yet know?

The MRC CoRE is working to identify the gaps in our knowledge, and to fill them where we can.  We want to work with other researchers across the world to create a system where we can all learn from each other. 

Each new therapy can build on the therapies that came before.  If we work together and share what we learn, we can all help patients get safer therapies more quickly.

One big challenge is time.

Sometimes there is only a short window when the treatment can really help the patient. If we wait too long, the medicine may no longer work as well.

Another challenge is that the patient’s genetic change may be very rare.

In some cases, the patient may be the only person in the world with that exact genetic mutation. This means we cannot test the treatment on other people first. 

There may be no good animal model to study the disease, or creating one could take too long. This makes it more difficult to develop and test potential treatments.

Even when an animal model does exist, there may not be enough time to run the usual, gold-standard animal studies.

Because of this, we have to think carefully about other ways to test the treatment.

• What tests can we do in the lab or on cells?
• What computer models or simulations can help?
• What level of evidence is strong enough to move forward while still keeping the patient as safe as possible?

First, we have to check the rules.

Do we have permission from regulators to use this combination of tools?

If not, do we have enough time, money, and resources to gather the safety information needed to get approval?

Next, we look at the facilities and people.

Are there places that can safely give the treatment?
Are there manufacturers who can make small, highly customized batches of the medicine to the highest quality?
Do hospitals or clinics have the right mix of specialist doctors, nurses, and enough beds?
Is any of this close enough to where the patient lives to make it practical?

Finally, we think about cost.

Can insurance or the national health system afford to provide this treatment?

First, we think about what the patient’s experience will be like.

• Will it involve complicated surgery or a long recovery?
• Will the treatment plan be hard to follow?
• Is the hospital or clinic far from where the patient lives?

Next, we look at the likely results.

• Could the treatment fully cure them, help only some symptoms, or maybe even make things worse?

We also consider how it might affect them and the people around them.

• How will it impact their emotions, body, daily life, and relationships?
• What about their family, carers, and friends?

We want to give people the information they need to make a decision about whether this treatment is right for them.

The MRC CoRE is working to involve patients, families, and advocacy groups in the discussion, at every stage of the development process.

There are over 4,500 diseases that might be treatable with this approach: much more than any one group can do.  We need to share what we learn as widely as possible.

Data sharing is complicated: we want to be as open as possible, but if we make everything “fully” public, it might be impossible for anyone to patent technologies built on top of our platform – which reduces incentive for companies to get involved.  

We need new models of licensing that will allow us to make our data and tools available to everyone who needs them, without tying anyone’s hands.

How do we work with regulators, to ensure that we are not cutting corners, but allowing us to get medicines to patients MUCH more quickly and cheaply than the current standard? Regulatory approval usually takes 2-4 years, and costs millions of pounds for each medicine.

How can we make sure that it counts as “medicine” (which insurance companies and the NHS can pay for) rather than “experimental” therapy (which is not reimbursable, and puts these therapies out of reach for most patients)?

How do we think about, and communicate, risk to patients and their parents?

Should the healthcare system do more or different types of genetic screening? Have they got the resources to deliver it?  How will the data be kept and used?

Will healthcare providers have the space and training to deliver these therapies?

Will ordinary clinicians be equipped for these conversations?

In the MRC CoRE, some of our research publications refer to patients with autism.  This word can mean different things in different contexts.

Our research focuses specifically on profound autism: people who are nonverbal or severely verbally limited, have significant intellectual disability, and are dependent on full-time care.  

We are not seeking to "cure" neurodivergence or people with autistic traits: we support the UK National Autistic Society position that autism is not a learning disability or a mental health condition.  

Around a third of autistic people also have a learning disability, and we want to support those patients and their families.

This episode of the The Daily (by the New York Times) provides an excellent introduction to the complexities of defining autism.

This is a technology that allows us to precisely target a specific part of DNA, and to interact with it in some way (e.g. to cut out or replace a target section of DNA).

Our partners at the University of Berkeley Innovative Genomics Institute created a fantastic resource to explain CRISPR.  Designed for children or anyone starting from scratch, CRISPR Made Simple is your guide to the basics of DNA, genes, and gene editing.  https://innovativegenomics.org/crispr-made-simple/

Base Editing is the next level of precision, allowing us to change one single base of DNA out of the entire genome.

You can also read more on the Wikipedia pages for CRISPR-Cas9, CRISPR-Cas13 and Base editing.

Different organisations have slightly different definitions of genetic rare disease.

In the MRC CoRE, we are working on diseases that come from a problem with a single gene, and occur in fewer than one in 2,000 people.

By this definition, there are about 4,500 rare diseases. While each condition may be uncommon, about 1 in 13 people will have some kind of rare genetic disease, meaning nearly every family is touched by rare disease in some way.

The Rare disease education hub has a lot of helpful materials on this topic.

Gene editing works by interrupting or changing DNA.

ASOs and Oligos work by interfering with the way the DNA is expressed (that is - it changes the way your body follows the instructions that the DNA is providing).  

ASOs and Oligos can tell your body to make more or less of something, compared to what the original DNA instructed (this is called upregulation or downregulation).  For example, if you have one "good" copy of a gene and one "bad" copy, we might use ASOs to upregulate the good copy, or downregulate (or silence) the bad copy.  In some circumstances, we can also use ASOs or Oligos to change the instructions slightly (to make a protein that is not quite what the DNA is instructing the cell to make).

ASOs do not permanently change DNA.

As your cells are renewed, the ASO medication wears off and ceases to work.  Sometimes a short-term effect is all the patient needs (e.g. medication while an organ is developing, which is no longer needed once the organ is completely developed).  This can also make ASOs a safer option to test potential treatments, to make sure the new genetic instructions have the expected result before developing a more permanent editing-based therapy.

In some cases patients can have repeat doses, but over time the body may come to recognise the medicine as a foreign substance and stop the medicine getting to the cells where it is needed.

Read more on the wikipedia pages for ASOs and Oligos.