RNA research: Small molecules, big impact

RNA research illustration

Too tiny to be seen by the naked eye, genetic material called RNA could advance the treatment of cardiovascular disease. BHF Professor Andrew Baker explains his work to Sarah Kidner.

Chances are you’ve heard of DNA, the molecule that encodes and carries your genetic information. You’re less likely to have heard of RNA, another type of genetic material, yet increasing our understanding of it could lead to ground-breaking treatments for cardiovascular disease (CVD). So, what is RNA and can it really improve patient outcomes?

Professor Andrew Baker, BHF Professor of Translational Cardiovascular Sciences, thinks it can. To that end, he is pioneering RNA-based research, backed by a £1.47m BHF grant. “The human genome is more complicated than we originally thought,” says Professor Baker. “Humans have approximately 25,000 genes, the same as many other species – so it is clear that human complexity derives from somewhere else.”

Understanding vascular disease

He believes RNA (short for ribonucleic acid) could play a vital role in regulating the everyday functions of the body (homeostasis) or in the development of diseases, including those of the vascular system. “We want to understand how normal blood vessels function when they’re healthy. That will help us to understand what happens when a disease process starts evolving,” explains Professor Baker.

Knowing how RNA causes diseases could lead to the creation of drugs that block or slow their development

He thinks RNA may be responsible for the rapid multiplication of cells within vessels that occurs following a bypass. This can lead to a re-narrowing of the artery and cause a recurrence of symptoms.

“We are particularly interested in how the blood vessels may become damaged in response to an injury resulting from a procedure such as a stent insertion or bypass surgery that causes a higher blood pressure in the blood vessel,” adds Professor Baker.

The team has also been exploring the role of microRNA (miRNA) in pulmonary arterial hypertension (PAH), a rare and devastating condition of the blood vessels in the lungs that can lead to heart failure. Working with researchers at Glasgow and the University of Cambridge, they have identified a molecule called microRNA-145 that is important in the development of PAH.

Knowing how RNA causes diseases could lead to the creation of drugs that block or slow their development. “We have published quite a lot on these strategies that could be new therapies, and we have filed a patent relating to a strategy that blocks the development of PAH,” says Professor Baker. “We are also actively assessing how this type of RNA can control the development of renal disease, supported by Kidney Research UK and the BHF.”

Translational studies

However, getting research out of the lab and to a point where it can benefit patients is hard work. “This is quite in-depth molecular biology, [but] I have an excellent team that is in the lab working to discover which RNA molecules are important,” says Professor Baker.

“Once we’ve identified RNA we think is important, we look at cells in a petri dish so we can see the way that cells multiply down a microscope and we can monitor whether they live and how they behave.”

My team loves coming to work; we want to discover new things

Once they’ve established the effect that a molecule has on the disease process, the team can progress to mouse models, then trials in larger animals, and from there go to clinical trial.

“That’s what we’re good at: we can take proof of concept from the cell culture and mouse models through to larger models and possible clinical trials. That’s what the BHF wants us to do, and that’s why I have my title as a translational vascular scientist, because we want to take these new therapies through to patient care,” Professor Baker says.

“We’re not going to do the translational side within the current programme grant, but if things look good, we’ll apply to the BHF for more money quickly to try to translate them.”

He’s optimistic that the work he and his team are doing will help fight CVD. “We’re able to get to grips with what’s going on in terms of RNA function in vascular disease, and we’re in a very good position to carry those through,” says Professor Baker. “Every day is different; it’s at the cutting edge and it’s a completely new area. My team loves coming to work; we want to discover new things and have an impact on patients. It’s thanks to donations to the BHF that we can.”

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Professor Andrew Baker

Professor Andrew BakerProfessor Baker is BHF Professor of Translational Cardiovascular Sciences at the University of Glasgow. He leads a team of scientists aiming to ‘translate’ discoveries made in the laboratory into new treatments for heart patients, including those who suffer from angina.

Over the past decade, Professor Baker has built up vast knowledge of how to use genes to treat diseases (gene therapy) and is embarking on the first ever gene therapy trial for heart bypass patients.

He is also investigating the potential of tiny pieces of genetic material, called microRNAs, in preventing complications after heart surgery.

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