Messenger ribonucleic acid, or mRNA for short, is a single-stranded molecule that carries genetic code from DNA to a cell’s protein-making machinery. Without mRNA, your genetic code wouldn’t be used, proteins wouldn’t be made, and your body wouldn’t work. If DNA is the bank card, then mRNA is the card reader.
Once a virus is inside our cells, it releases its own RNA, tricking our hijacked cells into spewing out copies of the virus – in the form of viral proteins – that compromise our immune system.
The mRNA vaccines
Traditional vaccines work by injecting inactivated virus proteins called antigens, which stimulate the body’s immune system to recognise the virus when it reappears. The genius of mRNA vaccines is there’s no need to inject the antigen itself.
Instead, these vaccines use the genetic sequence or “code” of the antigen translated into mRNA. It’s a ghost of the real thing, fooling the body into creating very real antibodies. The artificial mRNA itself then disappears, degraded by the body’s natural defences including enzymes that break it down, leaving us with only the antibodies.
It is, therefore, safer to produce, more quickly and cheaply, compared with traditional vaccines. A lab could make “a million doses of mRNA in a single 100ml test tube,” says Blakney.
The US Food and Drug Administration approved the Pfizer-BioNTech Covid-19 vaccine on 11 December, 2020, making history as not only the first ever mRNA vaccine approved for humans but also as the first to have a 95% efficacy rate in clinical trials. Approval of the Moderna mRNA vaccine followed close behind on 18 December. The previous title holder for “fastest ever vaccine”, the mumps vaccine, took four years. The Moderna and Pfizer–BioNTech vaccines took just 11 months.
The theory behind the mRNA vaccine was pioneered by University of Pennsylvania scientists Katalin Karikó and Drew Weissman, who both recently received the 2021 Lasker Award, America’s top biomedical research prize. Even in 2019, however, mainstream mRNA vaccines were believed to be at least five years away.
Improvement in the medical field
The pandemic fast-forwarded this field of medicine by half a decade. Kathryn Whitehead, an associate professor of chemical engineering and biomedical engineering at Carnegie Mellon University, and a key collaborator of Weissman and Karikó admits, “there weren’t many people in the mRNA therapeutics world who would have imagined 95% initial efficacy rates in this emergency scenario”.
At the University of Rochester, Dragony Fu, associate professor, department of biology, received expedited funding for his laboratory from the National Science Foundation to research RNA proteins.
Yizhou Dong, associate professor of pharmaceutics and pharmacology Ohio State University, specialises in little balls of fat, or lipids, needed to house the mRNA and safely deliver it to the cells without being immediately destroyed by our body. Lipids have been described as the “unsung hero” – without lipid delivery being finally perfected and approved in 2018, there would have been no Covid-19 mRNA vaccines by 2020.
Before Covid-19, there were many research studies looking at broader applications of combining this new lipid delivery technique with mRNA Dong says, including genetic disorders, cancer immunotherapy, infectious diseases and bacterial infections. “As long as you have the antigen and can sequence the protein, theoretically it should work”.
Solutions for tropical diseases are being explored
Moderna is close to phase two (out of three) in clinical mRNA vaccine trials for both Zika and Chikungunya. Both are described as “neglected”, so-called because they effect the poorest populations of the world and do not receive adequate research and funding. The speed and cost of mRNA vaccines could change that paradigm and signal the end of neglected tropical diseases.
Perhaps the first new mRNA vaccine to hit our shelves, however, will be for a more familiar foe – the flu. Influenza viruses are responsible for an estimated 290,000–650,000 deaths annually worldwide.
“We’re most likely to see mRNA vaccines against influenza in the near future,” says Whitehead. “These mRNA vaccines have been in development for years, and clinical trials to date have been encouraging. There are currently five clinical trials for Influenza A, including one in phase two”.
There’s also the potential to mix various mRNA vaccines together into a single health booster vaccine, which could ward off cancers and viruses at the same time.
Currently we need regular booster shots – and these shots tend to hurt your arm, sometimes with fatiguing side effects. At the time of writing, we are less than a year into real-world use.
Anaphylactic reactions (albeit with no deaths) have been observed in approximately 2 to 5 people per million vaccinated in the United States: slightly higher, 4.7 per million, with the Pfizer–BioNTech vaccine compared to 2.5 per million vaccinations from the Moderna vaccine. According to one analysis, while still low, this is 11 times higher than with the flu vaccine.
Self Amplifying mRNA
Blakney’s lab at UBC is, however, working on an answer: saRNA, or self-amplifying mRNA. It has the same structural components as normal mRNA, except once inside a cell it can make copies of itself.
This means more bang for your buck, and less pain in your arm. In a tortoise versus hare race, mRNA vaccines may have run ahead to combat Covid-19, but saRNA may win out in the end – and indeed has just received $195m (£145m) backing from AstraZeneca.
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