Could mRNA make us superhuman?

Until recently most people had never even heard of mRNA vaccines. Now scientists believe they may be the key to solving a wealth of health problems.

Barely a year ago, Anna Blakney was working in a inconspicuous, niche field of science in a lab in London. Few people outside of her scientific circles had heard of mRNA vaccines. None yet existed. Today, she's in demand. She was in the right place at the right time to ride a once-in-a-generation wave of scientific progress. She even gave this new era a name: "the RNAissance".

Due to the Covid-19 pandemic, many people have now heard of – and have received – an mRNA vaccine. When Blakney started her PhD at Imperial College London in 2016, "a lot of people were sceptical whether it could work". Now, "the whole field of mRNA is exploding. It's a game changer in medicine," she says. It raises some big, exciting questions: could mRNA vaccines provide a cure for cancers, HIV, tropical diseases, and even give us superhuman immunity?

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. 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 then disappears, degraded by the body's natural defences including enzymes that break it down, leaving us with the antibodies.

It is, therefore, safer to produce, more quickly and cheaply, compared with traditional vaccines. You no longer need huge bio-secure labs growing deadly viruses inside millions of chicken eggs. Instead, just one lab can sequence the proteins of the antigen and email it around the world. With that information a lab could make "a million doses of mRNA in a single 100ml test tube."

We've now seen that process play out in real time. On January 10, 2020, Zhang Yongzhen, a professor of zoonoses at the Chinese Centre for Disease Control and Prevention in Beijing sequenced the genome for Covid-19 and published the next day. Covid-19 was declared a pandemic by the WHO on March 11. On March 16, using Zhang's sequence, the first mRNA vaccine began its phase one clinical trial. The US Food and Drug Administration approved the Pfizer-BioNTech Covid-19 vaccine on December 11, 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 December 18. The previous title holder for "fastest ever vaccine", the mumps vaccine, took four years. The Moderna and Pfizer– BioNTech vaccines took 11 months.

The theory behind the mRNA vaccine was pioneered by University of Pennsylvania scientists Katalin Karikó and Drew Weissman. In 2019, mainstream mRNA vaccines were believed to be at least five years away. 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".

But now, the possibilities are seemingly endless. Or, as Blakney puts it: "It's worked for a viral glycoprotein, what other vaccines can we make with it? What can we do beyond that?"

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. If we are currently witnessing mRNA vaccine 1.0 for Covid-19, then 2.0 will address two further categories of disease, says Fu: "One is pathogens, like Sars, but you can apply this technology to other foreign invaders such as HIV. Already before Covid, companies were in development making mRNA vaccines against HIV." He also cites Zika, herpes and malarial parasites in the pathogens camp.

"The other category is autoimmune diseases," he says. "That is intriguing because it's verging beyond the strict definition of a vaccine." Fu says the future could involve mRNA "treatments", for example to reduce inflammation. "So many possibilities."

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 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 Covid19 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.

Thanks to the combined breakthrough in lipid delivery and mRNA technology, vaccines and treatments in development include Translate Bio's mRNA therapy's for cystic fibrosis and multiple sclerosis; Gritstone Oncology and Gilead Sciences' mRNA vaccine for HIV; Arcturus Therapeutics' therapies for cystic fibrosis and heart disease; and German start-up Ethris, with AstraZeneca, are developing mRNA therapies for severe pulmonary diseases and asthma.

Solutions for tropical diseases are being explored too. Moderna are close to phase two in clinical mRNA vaccine trials for both Zika and Chikungunya.

Several pharmaceutical companies are also pursuing mRNA vaccines and treatments for cancer. "Cancer cells have certain surface markers that the rest of the cells in your body don't have," says Blakney. “You can train your immune system to recognise and kill those cells, just like you can train your immune system to recognise and kill a virus: you just figure out what proteins are on the surface of your tumour cells and use that as a vaccine".

If treatments for cancer, HIV and tropical disease are coming along with mRNA 2.0, then what could be even further down the line with 3.0? One huge area of concern for modern medicine is antibiotic resistance. "You could envision making a vaccine against a bacterial antigen such as C difficile or some really tricky to treat bacteria," says Blakney. There's also potential for more general commercial health and wellbeing applications. Dong has run a successful mouse trial targeting cholesterol.

All this raises the question: could mRNA therapeutics give us almost superhuman immunity?