For many of us, mRNA technology triumphantly arrived on the scene in December 2020 when successful phase 3 trials of the Pfizer-BioNTech COVID-19 vaccine were announced, shortly followed by Moderna’s own announcement of successful phase 3 trials for its mRNA vaccine. However, mRNA technology has been around since the early 90s,1 with human trials of cancer vaccines using mRNA technology taking place since at least 2011.2 In this article, we’ll look why this emerging biopharma technology was perfectly placed to solve the COVID-19 vaccine puzzle, and the transformative role it’s set to play in healthcare beyond the pandemic.

Understanding mRNA COVID-19 Vaccines

The data from phase 3 human trials for both the Moderna and Pfizer-BioNTech vaccines was overwhelmingly positive, reporting over 90% effectiveness. Excitement at the prospect of a route out of the pandemic was quickly followed by questions over how it was possible to produce effective vaccines in such a short time. Vaccine research and development can typically take 10 – 15 years,3 and the public were warned that the best they should hope for is 1 – 2 years for a COVID-19 vaccine, assuming all five stages of the vaccine development process went smoothly.

After the publishing of the SARS-CoV-2 virus sequencing in January 2020 by Chinese scientists, the race began to create a vaccine. The Pfizer-BioNTech phase 3 trial results were announced less than 12 months after the first cases were reported in China, and roughly 10 months after the crucial sequencing data was published, making its speed to market a new world record.4

Several factors allowed for significant increase in speed: limitless funding, unprecedented collaboration within the biopharma world, and intensified and overlapping R&D processes, including overlapping human trials to name a few. Another key factor behind the speed to market of the Moderna and Pfizer-BioNTech vaccines is that they utilise a relatively new biopharma technology: messenger ribonucleic acid, or messenger RNA (mRNA).

Traditionally, vaccines are developed by weakening or killing a virus, or by producing part of the virus in the lab. However, this is time consuming.5 Unlike traditional vaccines, mRNA vaccines don’t use anything of the actual virus, instead replicating the virus’ genetic code synthetically, which is then introduced into the human body. This genetic code then encourages the human body to produce the SARS-CoV-2 spike protein, which then triggers the crucial immune response, protecting the host.

Because mRNA technology has been in live animal and human trials for at least a decade, it’s relatively safe and straightforward to encode it with the relevant antigen genetic code, allowing for rapid development. As a result, it could take as little as a week to create a vaccine and begin initial testing.6

The success of the Moderna and Pfizer-BioNTech mRNA vaccines has shown the world what’s possible: we now have a biopharma technology capable of meeting unforeseen human health emergencies quickly and effectively. But what does the emergence of mRNA technology mean for biopharma and healthcare beyond COVID-19?

mRNA Technology Before COVID-19

mRNA technology first reared its head in the early 90s, but with limited endorsement. Chief architect of mRNA technology, Katalin Karikó, a biochemist born in Hungary, now working at the University of Pennsylvania, spent years fighting a losing battle in the search for funding. Her theories made perfect sense: the human body naturally produces millions of the tiny proteins in order to keep itself alive, and it uses mRNA to instruct cells which proteins to make. Her theory was to create our own, specific mRNA, in theory allowing you to synthetically instruct the body to produce any number of protein types, triggering whichever targeted immune response you desire.7 Compelling science with potentially world-changing implications, yes, but it had a key stumbling block.

Like DNA, each RNA strand has the same basic structure, composed of nitrogenous bases covalently bound to a sugar-phosphate backbone.8 Each one of these strands is made up of four building blocks, known as nucleosides. Here in lay a problem for early mRNA technology. In their synthetic, altered form, one of these building blocks was acting as a ‘red flag’ when introduced into a living host, initiating an unwanted immune response, destroying the mRNA before it could arrive at the intended cells.9 For mRNA science to proceed beyond the conceptual, it’d need to solve this issue. So it was, that Katalin Karikó and her long-time collaborator, Drew Weissman, an immunologist with a medical degree and Ph.D. from Boston University, devised a solution. By simply swapping out the troublemaking block for a tweaked version, the mRNA was able to sneak past the body’s natural defences, thus reaching its intended goal.

mRNA technology had arrived. Fast forward to 2017, and soon-to-be world known German biotech company, BioNTech had published results from the first clinical trial for an mRNA-based individualized vaccine with the potential to target all cancer types.10 To create the vaccines, the researchers sequenced the patient’s tumour DNA and identified tumour mutations by comparing it to the DNA of healthy tissue. Then, an algorithm identifies which mutations are more likely to be recognised by the immune system and generate an immune response, and those selected are engineered into an mRNA vaccine.11

Of the 13 patients to participate in the human trial (all of whom had had cancer, recovered, and had a history of relapsing with less and less time between each recovery), eight patients remained completely cancer free throughout the 23-month period after receiving the vaccine. Of the five patients who had relapsed before the trial started, one of them saw their tumour disappear completely after being vaccinated, and another saw their tumour shrink significantly. The remaining three did not respond to the vaccine.12

mRNA Beyond COVID-19: Cancer, Heart Disease, HIV and More

mRNA technology is tipped to change medicine and the pharmaceutical industry as we know it.13 This highly adaptable, quick to market, and intelligent technology which effectively instructs the human body to produce its own vaccine and treatments is being studied to treat heart disease, cancer, and other infectious diseases,14 and has applications in the fields of HIV and common flu treatments as well.

One of mRNA’s great strengths is that it is highly targeted, with scientists able to program mRNA to target specific proteins that will then instruct the body to commit to the desired immune response, tackling the disease or illness head on. And, because flu, cancer, HIV and infectious diseases such as COVID-19 have numerous strains and types, and are liable to shift and evolve to fight off treatments, mRNA technology is ideally placed to quickly and accurately create targeted treatments and vaccines whenever new strains arise, or different immune responses need to be encouraged.

Perhaps the most significant application for mRNA technology is in the fight against cancer. With human trials into personalised cancer vaccines in place pre-COVID-19, the movement towards mRNA treatments in cancer care was already well underway. One potential silver lining to the COVID-19 pandemic is the vastly increased funding and scientific spotlight being shined upon mRNA technology, which will hopefully accelerate its development and practical application.

In a recent interview on the subject of mRNA technology in cancer treatments, Dr. John P. Cooke, a physician-scientist with Houston Methodist Hospital and an expert in mRNA technology said: ‘Cancers can proliferate and metastasize and kill you because they evade immune surveillance. That is, they evade the white blood cells that are meant to get rid of cancer. Every cancer is different because cancers are in large part derived from cellular mutations and mutations maybe are often very different from one tumour to another. Every person has their own tumour.’15 Just like with COVID-19, scientists can sequence the mRNA with an individual person’s own tumour, and then deliver a targeted, personalised treatment that would instigate the desired immune response.

In the same interview, Cooke went on to say: ‘I think we’re at the dawn of a whole new therapeutic arena. It’s going to be a whole new industry and it’s going to give us limitless possibilities for treating diseases that were undruggable. RNA will allow us to treat many that were heretofore untreatable.’16

The Role of Cold Chain

As the influence of mRNA technology grows, and its applications become more and more common, so too will the role of cold chain logistics. As has been widely reported, mRNA technology does come with its challenges, specifically the need to keep these highly sensitive biologics at very cold temperatures – as low as -70°C. Failing to keep these products at the specified temperatures can lead to loss of some or all efficacy, rendering these highly expensive treatments and vaccines useless.

Working with experienced designers and manufacturers of temperature-controlled packaging will become an increasingly important part of getting mRNA biopharmaceuticals to market, with the risks attached to getting cold chain wrong far too great to take. Every step, from R&D, international flights, and local, last mile delivery, will need to consider the role of temperature control in order to support effective mRNA delivery.

ORCA Packaging Product Range

At Intelsius, we design, test and manufacture temperature-controlled packaging perfectly suited to shipping highly sensitive biologics anywhere in the world, from large scale freight to small scale last mile delivery. As mRNA vaccines and treatments become more prevalent, the demand for our products and services will increase. We’re already actively participating in the roll out of the Pfizer-BioNTech and Modern mRNA COVID-19 vaccines in Spain, with vaccines being transported in our ORCA range of temperature-controlled packaging.

To find out more information about how we can support your cold chain needs, speak to a member of our dedicated customer service team by contacting your local branch here.

Alternatively, you can read about our ORCA range of temperature-controlled packaging on our website, here.

External References
  1. Science Direct (2019) – Three decades of messenger RNA vaccine development
  2. European Commission (2020) – Five things you need to know about: mRNA vaccine safety
  3. World Economic Forum (2020) – 5 charts that tell the story of vaccines today
  4. UCLA Health (2020) – The fastest vaccine in history
  5. The Guardian (2020) – How has a Covid vaccine been developed so quickly?
  6. Pfizer (2020) – BEHIND THE SCIENCE: WHAT IS AN MRNA VACCINE?
  7. Stat News (2020) – The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race
  8. Scitable (2008) – Chemical Structure of RNA
  9. Stat News (2020) – The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race
  10. Labiotech (2017) – Results are in from the First Human Trial of an Universal Cancer Vaccine
  11. Labiotech (2017) – Results are in from the First Human Trial of an Universal Cancer Vaccine
  12. Labiotech (2017) – Results are in from the First Human Trial of an Universal Cancer Vaccine
  13. Entrepreneur (2020) – Moderna Designed a Covid-19 Vaccine in Just Two Days Thanks to mRNA Technology
  14. Forbes (2021) – The ‘New Normal’ And The Future Of Technology After The Covid-19 Pandemic
  15. Healthline (2020) – New mRNA Technique Used on COVID-19 Vaccine May Lead to Flu, HIV Vaccinations
  16. Healthline (2020) – New mRNA Technique Used on COVID-19 Vaccine May Lead to Flu, HIV Vaccinations
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