Complex Made Simple

Synthetic mRNA used today as a vaccine promises a disease-free future beyond COVID-19

The dream of mRNA persevered in part because its core principle was tantalizingly simple, even beautiful: The world’s most powerful drug factory might be inside all of us

mRNA commandeers our cellular machinery to make just about any protein under the sun A similar RNA-based technology was used to vaccinate against malaria , a devastating disease Cancer studies represent all the 21 ongoing mRNA human trials outside of infectious diseases

Synthetic mRNA’s story stretches far beyond this pandemic.

The technology behind the Pfizer-BioNTech and Moderna vaccines was in fact more than 40 years in the making from when a Hungarian scientist pioneered early mRNA research.

The dream of mRNA persevered in part because its core principle was tantalizingly simple, even beautiful: The world’s most powerful drug factory might be inside all of us.

mRNA, which stands for messenger ribonucleic acid, tells our cells which proteins to make and theoretically commandeer our cellular machinery to make just about any protein under the sun. 

You could mass-produce molecules that occur naturally in the body to repair organs or improve blood flow. Or you could request our cells to cook up an off-menu protein, which our immune system would learn to identify as an invader and destroy.

Currently, mRNA vaccines send detailed instructions to our cells to make their distinctive “spike protein.” Our immune system, seeing the foreign intruder, targets these proteins for destruction without disabling the mRNA. 

Later, if we confront the full virus, our bodies recognize the spike protein again and attack it with the precision of a well-trained military, reducing the risk of infection and blocking severe illness.

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mRNA Beyond the Vaccine

This year, a team at Yale patented a similar RNA-based technology to vaccinate against malaria, perhaps the world’s most devastating disease. Because mRNA is so easy to edit, Pfizer says that it is planning to use it against seasonal flu, which mutates constantly and kills hundreds of thousands of people around the world every year. 

BioNTech is developing individualized therapies that would create on-demand proteins associated with specific tumors to teach the body to fight off advanced cancer. 

In mouse trials, synthetic-mRNA therapies have been shown to slow and reverse the effects of multiple sclerosis.  

Researchers have been incredibly optimistic about mRNA vaccines’ potential in a wide range of viral diseases, from curing birth defects, to HIV and hepatitis C.   

Immuno-oncology is by far the busiest therapeutic area for mRNA vaccine development, with cancer studies representing all the 21 ongoing mRNA human trials outside of infectious diseases, according to GlobalData.

Large pharma firms are starting to forge partnerships to get involved in the mRNA immune-oncology space, from Merck’s strategic collaboration with Moderna to Roche’s alliance with BioNTech. 

Innovative biotechs joining forces with Big Pharma is particularly appropriate as many personalized cancer vaccines are intended to be used alongside existing cancer treatments such as Merck’s Keytruda and Roche’s Tecentriq.

These early days of mRNA cancer vaccine research (no project has reached further than Phase II trials so far) have been littered with disappointing trial results, but there have been rays of hope for future breakthroughs in mRNA cancer vaccines, most notably Moderna’s mRNA-4157.

The project is in a small Phase I study of ten patients with head and neck squamous cell carcinoma achieved a response rate of 50% in combination with Merck’s Keytruda, positive results that the biotech will be hoping can be replicated in later-stage trials with larger patient numbers.

How the COVID-19 mRNA vaccines work

COVID-19 mRNA vaccines give instructions for our cells to make a harmless piece of what is called the “spike protein.” The spike protein is found on the surface of the virus that causes COVID-19.

Once the instructions (mRNA) are inside the immune cells, the cells use them to make the protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them.

Next, the cell displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19.