We can all agree that 2020 has been a difficult year, but a silver lining was two women winning the Nobel Prize in Chemistry for developing the tools to edit DNA in living cells. Known as -Cas9 (often shortened to ), their discovery of “genetic scissors” has revolutionised science as we know it and holds the promise of being able to treat or even cure diseases – from heart muscle problems to coronary heart disease.

How are heart researchers using the Nobel Prize-winning genetic scissors?

A cut above the rest

There is enormous power in being able to cut out, replace or turn off bad genes whenever we want – especially if that power is used to heal. Take BHF-funded researcher Dr Emily Noël for example. She’s using the genetic scissors to find out why mutations (or faults) in genes can cause babies to be born with heart defects.

At the University of Sheffield, Dr Noël and her team are looking at how congenital heart disease develops, in particular studying the role of the cytoskeleton. Like the bricks and walls of a building, the cytoskeleton is the ‘frame’ of the cell, providing support, keeping structures in place, and giving the cell a definite shape.

If the cytoskeleton is not organised properly, for example from a faulty gene, heart cells and the heart itself will not form normally, leading to babies born with heart problems.

Dr Noël and her team will use to change or remove cytoskeleton genes in zebrafish – whose heart develops in a similar way to humans. In doing so, they will work out which heart cells require these genes, what they do in the cells, and what happens when the genes do not work normally – which will ultimately help us to understand more about why people with faults in their cytoskeleton genes can develop heart defects.

How are heart researchers using the Nobel Prize-winning genetic scissors?

A PhD student working with Dr Noël will also use in zebrafish to study why faults in molecules called Dock6 and Eogt can cause heart problems in people with Adams-Oliver syndrome (AOS). AOS is a rare inherited disorder characterised by defects of the scalp and abnormalities of the arms, fingers, legs or toes – with approximately 20% of babies born with the condition also having a heart defect.

It’s cutting-edge technology

A bit further south, at the University of Keele, we have awarded funding to Dr Vinoj George who will use the power of to study an inherited disease of the heart muscle called arrhythmogenic right ventricular cardiomyopathy (ARVC).

In ARVC, faulty genes stop heart muscle cells (or cardiomyocytes) from sticking together correctly. As a result, the cells die and are replaced with fatty scar tissue, preventing the heart from pumping blood properly and causing abnormal heart rhythms.

Combining with a technology called optogenetics (which uses light to control cell behaviour), a PhD student working with Dr George will create 3D models of ARVC. First, they will introduce a mutation associated with severe ARVC into human stem cells, which have the potential to develop into any type of cell in the body. They will then allow the stem cells to grow into mature heart muscle cells on a 3D frame or scaffold.

It might sound like science fiction, but new knowledge obtained from these models could help us to identify genetic differences linked to more severe forms of ARVC and reveal new ways to combat this disease.

A pair of genes

Even further south, at the University of Birmingham, a PhD student working with Dr Neil Morgan is using to study thrombocytopenia – a condition where someone has low levels of platelets in their blood. Platelets are cell fragments which can clump together to form a blood clot after an injury and so prevent excessive bleeding. People with thrombocytopenia can be prone to bruising, bleeding gums and nosebleeds as their blood is less able to clot.

Dr Morgan and his team discovered that some people with this condition have faults in a gene called SLFN14. Using to edit the gene in platelets in mice, the BHF-funded researchers will now study how SLFN14 controls platelet formation and function. Ultimately, the results from this and similar studies will help us to understand more about how to treat bleeding disorders.

How are heart researchers using the Nobel Prize-winning genetic scissors?

At Imperial College London, BHF-funded researcher Dr Christopher Rhodes and his team are working on a project looking at pulmonary arterial hypertension (PAH) – a condition where the pressure in the blood vessels supplying the lungs rises, which can ultimately lead to heart failure. PAH can be hereditary (passed down in families), and unfortunately, there is currently no cure for it except for heart and lung transplants.

Dr Rhodes and his team previously identified faults near a gene called SOX17 in people with heritable PAH. Using in human blood vessel cells, mice and rats, the researchers will now introduce or remove mutations near the SOX17 gene to see how this influences blood vessel function and the development of PAH. They will also test whether different drugs can correct the effects of the faulty gene – providing hope that in the future this type of treatment could be used to help people with PAH.

With shear power

At the University of Oxford, Professor Paul Riley and his team are using to find out how to repair heart damage after injury, specifically looking at the heart’s ability to regenerate itself – like that of a superhero in a science fiction movie.

For many years, this team has been studying cells in the epicardium – the outer layer of the heart known to be important for heart development. Their thinking is that if these epicardium cells could be switched on in adults who have sustained a heart injury, it may be possible to encourage the heart to repair itself.

Studying adult zebrafish and newborn mice – both of which can regenerate their hearts – the team aim to identify molecules in the epicardium that are important for ensuring heart repair in both species. If a molecule is identified as important in both zebrafish and mice, then it’s more likely to have a potential role in humans too. One way they will do this is by using to remove selected genes in epicardium cells.

Ultimately, their aim is to pinpoint molecules that, if targeted with drugs, could promote natural heart repair in people who have had a heart attack – a medical emergency at the root of around 200,000 hospital visits each year in the UK.

How are heart researchers using the Nobel Prize-winning genetic scissors?

Yes, we can all agree that 2020 has been a year like no other, but the fact that there are researchers out there using a Nobel Prize-winning discovery to help us beat heartbreak forever – to help us live in a world free from the fear of heart and circulatory diseases – is exactly what we all needed to know right now.

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