mRNA therapies to stop heart disease

Associate Professor Xiaowei Wang wants to stop heart disease. To reach this goal, Xiaowei is developing mRNA therapies. She uses nanoparticles in nasal spray and with ultrasound to target these therapies to disease sites in the body.

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mRNA therapies tell cells to build proteins that stop disease

mRNA stands for messenger RNA, which helps translate DNA code to create the building blocks of life. It does this by carrying messages containing sections of DNA code from the nucleus of cells to the cell machinery. This machinery reads the code and translates it into proteins.

Researchers can harness mRNA to create medical therapies. They design mRNA to tell cells to build proteins that stop disease.

Using mRNA to stop heart disease from starting or getting worse

Xiaowei is designing mRNA to stop inflammation in blood vessels and blood clotting. She hopes this will stop heart disease from starting or getting worse.

Inflammation is one way our immune system fights pathogens. Toxins in the body caused by smoking, heavy alcohol use, fatty diet, high salt content and stress can trigger chronic inflammation.

This immune system response can cause more damage in the body. Chronic inflammation damages the inner lining of blood vessels. Inflammation also walls off fatty plaque inside the arteries which can then rupture and form a blood clot. These chronic conditions can cause a heart attack or stroke.

‘If you can stop inflammation, then you can stop a lot of these downstream effects that would happen later on,’ Xiaowei explains.

The CD39 protein stops inflammation and blood clotting

Xiaowei identified a protein in the body called CD39 that stops inflammation and blood clotting. But CD39 also has a negative side effect: it causes bleeding. For this reason, ‘you can’t give CD39 to patients as a dose of medicine,’ Xiaowei tells us.

Xiaowei wants to use mRNA to deliver the CD39 protein directly to disease sites in the body. ‘That would allow us to bypass all the bleeding complications,’ she says.

Targeting mRNA to disease sites

The team is making CD39 mRNA nanoparticles to tell the body to make CD39 proteins.  The next step is to deliver the mRNA to cells at the disease site. This allows the mRNA to tell the cells to make CD39 proteins where the body needs them.

Xiaowei is testing 3 delivery methods in mice:

  • for fatty plaque in arteries (atherosclerosis), immune cells engulf the mRNA nanoparticles and transport them to the disease site.
  • for high blood pressure in the lungs (pulmonary hypertension), nasal spray delivers the mRNA nanoparticles to the disease site.
  • for weakness in the main blood vessel in the abdomen (abdominal aortic aneurysm), antibodies transport mRNA ultrasonic-nanoparticles to the disease site. A technologist uses ultrasound to release the mRNA particles.

The first step to building a vaccination for heart disease

‘Cardiovascular inflammation is complex,’ Xiaowei says. ‘To block inflammation, you might need a cocktail of different mRNA that all work towards minimizing risks of disease.

‘This research is only looking at one target, the CD39 protein. To build a vaccination for heart disease we have to work step by step, looking at each potential target individually.

‘This is not a one-person project. We are working with global partners to move this project forward.’

From technologist to researcher

Xiaowei began her career as a cardiac technologist. ‘I was working in a hospital where patients with heart attack have catheterisation to open their arteries. I was on the front line where I saw how people suffer.

‘I thought, we have all these fancy imaging technologies that we use to diagnosis disease. There must be something that we can do to prevent disease and not just wait until the complication has already happened. That started me on this research pathway.’

The MRFF granted $690,000 to Xiaowei’s research.

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