The discovery of ‘dark matter’ has opened up a whole world of possibilities for therapeutics and even changed the way we look at biology. Samir Ounzain explains some of the opportunities and challenges that lie ahead.

When we sequenced the human genome in 2001, we discovered that 98% of our DNA is ‘dark matter’. Unlike the proteins that make up your body or cells, dark matter doesn’t encode protein-coding genes and therefore has no obvious function. Because of this, it was dismissed as ‘junk DNA’.

Over the last couple of decades, however, we’ve come to understand that these non-coding sequences of our DNA are anything but junk. In fact, we can think of this dark matter as the software that tells our genes how to behave in response to our environment and behaviour. It’s the interface between the outside world and what happens in our cells. This is extremely significant – in fact, it’s a huge part of what distinguishes human beings from simple organisms. It’s this dark matter that allows for complex patterns of gene expression, making the highly developed cellular and organismal traits of human beings possible.

Once the human genome had been sequenced, biology went digital. With the ‘book of life’ at our disposal, we could start to compare the genetic code of millions of individuals and look at genetic variations, or mutations, that lead to common diseases and traits. We found that almost all these mutations happen in dark matter. Once we’d realised that dark matter responds to lifestyle and environmental factors, the link between dark matter and diseases also became clear. The logical implication of this is that drugs and therapeutics can be developed to act on non-coding DNA to control changes in the cell behaviour that causes common and chronic conditions. RNAs, which are issued from DNA, are in charge of regulating processes within our cells. Therefore, targeting or leveraging non-coding RNA could be crucial to develop new solutions to prevent or cure diseases.

At HAYA Therapeutics, our main focus is heart disease. We’ve mapped a whole galaxy of non-coding DNA – and more importantly, the non-coding RNAs it produces – that are in involved in heart disease, and in particular heart failure, which is driven by tissue scarring or fibrosis in the heart. When the heart is exposed to lifestyle and stress factors, tissue cells change their identity and become ‘activated fibroblasts’. We discovered what controls this process, which means we can use dark matter to stop fibrosis occurring within the heart – and thus prevent heart failure.

Even with all the advances of recent years, we’ve still only scratched the surface of what the discovery of dark matter might mean. The human genome comprises three billion letters and 98% of it is dark matter. New technologies such as AI could transform the landscape of what we can do in this field. In ten years, it will be possible to read, write and reprogramme dark matter, and this will accelerate the diagnosis and prevention of many common and chronic diseases, such as diabetes, obesity, cardiovascular disease and cancer.

We don’t yet have effective therapies for many of the most common diseases, but once we figure out the exact mechanisms that will enable us to target them, dark matter could be the key to changing that. To progress in the field, we need to look to biology. Biology tells us that dark matter is what programmes disease, so this is where we need to focus our attention. Like everyone else, scientists tend to stick to what they know, and one thing the industry really does know well is proteins and how to make drugs that act on them. But proteins represent only 1.8% of the genetic information within us. Let’s not ignore 98% of our DNA – and all the RNAs it produces!

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