The huge potential of mRNA technology

The new technology made its name when it delivered Covid-19 vaccines in record time. But it could be pressed into use in many other areas too. Simon Wilson reports.

What are mRNA vaccines?

Conventional vaccines work by training the immune system to recognise and fight viruses or bacteria by introducing an inactivated form of a virus (one that has been rendered harmless) into a patient’s body. However, the biotechnology used in the mRNA vaccines made by Pfizer/ BioNTech and Moderna is fundamentally different. The aim is the same: to train the immune system to recognise and fight off the virus. But these new vaccines accomplish this by using synthetic “messenger RNA” to deliver a snippet of viral code to your body in order to teach your immune system what the relevant disease-causing virus looks like. Then, if your system encounters the virus, your body is primed to mount a defence using specialised antibodies and T-cells.

What exactly is mRNA?

Messenger RNA (ribonucleic acid) is a polymeric molecule – naturally produced and essential to all known forms of life – whose principal job is to tell cells which proteins to make. To make an mRNA vaccine, scientists produce it synthetically in a laboratory. When injected, the synthetic mRNA goes to an area of the body’s cells called the cytoplasm, where it is turned into proteins that look like the relevant proteins of the virus. This primes the cells to help them fight off infection if your body later encounters the real thing.

Is the technology new?

It has been in development since the late 1970s – going through numerous hurdles and breakthroughs over the decades but never before authorised for use. Katalin Karikó, the Hungarian-born, US-based biochemist who pioneered mRNA research in the 1980s, is now a senior adviser to BioNTech.

In early 2020, scientists there and at Moderna, who had been researching potential mRNA applications for influenza and cancer, were able to switch their focus within days of China sharing the genetic sequencing of the novel coronavirus – with results that far exceeded most expectations. 

The beauty of mRNA technology is the speed, in that once you have the genetic sequence, you can identify exactly what you need to put in the code of your vaccine, and you are giving instructions to the target that the immune system can respond to,” John Bowler, of the Schroder Global Healthcare Fund, told Bloomberg. “It really changes the whole dynamic on infectious diseases.”

What else is being developed?

While the Covid-19 vaccine rollout continues, the race for the next generation of mRNA therapies – targeted at a variety of other diseases – is already intensifying, says Stephen Buranyi in Wired. Moderna and BioNTech each have nine candidates in development or early clinical trials. There are at least six mRNA vaccines against flu in the pipeline, and a similar number against HIV, Nipah, Zika, herpes, dengue, hepatitis and malaria have all been announced. And the pharma giants are snapping up promising researchers for huge contracts. Sanofi recently paid $425m to partner with a small US biotech called Translate Bio; GSK paid $294m to work with Germany’s CureVac.

But the potential for mRNA is not limited to infectious diseases. There is also much excitement about the potential of mRNA in treating certain rare genetic diseases (caused by defects in or deficits of proteins) and cancer (targeting cancer cells in the same way that the immune system targets infection).

In the field of regenerative therapeutics, mRNA might also help in the growth of new blood vessels (in research by Moderna and AstraZeneca).

Will this make other vaccines obsolete?

It’s highly unlikely in the foreseeable future. First, not every current vaccine technology works for every target, and it’s highly unlikely that mRNA will prove effective – or the most cost-effective solution – in every scenario. Existing efforts to develop mRNA vaccines against other diseases (for example by Moderna and GSK in 2016 and 2017) have been much less successful than the vaccines developed successfully for Covid-19, and the reasons for that are not yet fully understood.

Second, there remain big issues to solve around stability and affordability of manufacturing if mRNA vaccines are to reach all corners of the world – and the shipping and super-cold storage of mRNA vaccines requires expensive infrastructure. That suggests a diversity of vaccine types will remain necessary. And third, where effective, cheap, established vaccines already exist, there’s no good reason for drugs companies to switch to a completely new platform. All that said, there’s no doubt mRNA vaccines have transformed the sector from the point of view of investors. 

Who’s doing well?

Moderna and BioNTech are the names everyone knows. However, rival CureVac’s near-50% stock slump in one day in June – on disappointing trial results for its mRNA Covid-19 vaccine  – is a good example of the sector’s risk. Other focused biotech firms using non-mRNA technology include Novavax and Dynavax (both in vaccines), while Vir Biotechnology is developing antibody treatments for Covid-19, says Suzanne Woolley on Bloomberg.

Any other tips?

In the wider supply chain – for example makers of the ingredients in vaccines, diagnostics and testing companies, and even makers of rubber stoppers, syringes or speciality glass products – businesses worth investigating include West Pharmaceutical Services, Becton Dickinson and Germany’s Gerresheimer, says Woolley.

Other possibilities are Catalent, which specialises in delivery technologies for drugs and biologics, and Corning, which makes vials. Germany’s Evonik Industries supplies lipids needed for the Pfizer/BioNTech vaccine. Spanish pharmaceutical company Rovi bottles Moderna’s Covid-19 vaccine and Switzerland-based Lonza produces some of the ingredients that Rovi bottles for Moderna.

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