Messenger RNA was, for decades, a biological curiosity with a frustrating problem: it was fragile, and the immune system reacted to it. The idea of using mRNA as a therapeutic — instructing cells to produce a protein of interest — was theoretically elegant but practically daunting. Then came COVID-19, and with it the fastest vaccine development in history. In under a year, mRNA vaccines from Pfizer-BioNTech and Moderna went from sequence to emergency authorisation, ultimately reaching billions of arms. The pandemic proved the platform. Now the harder question is what it can do next.
How mRNA Vaccines Work
An mRNA vaccine delivers a strand of messenger RNA encased in lipid nanoparticles. The RNA carries instructions for a target protein — for COVID, the SARS-CoV-2 spike protein. Cells take up the nanoparticles, read the RNA, and produce the protein, which the immune system recognises as foreign and mounts a response against. Crucially, the RNA never enters the cell nucleus and never integrates into the genome; it is transient, degraded within hours or days.
The platform’s advantages are speed and flexibility. Once a sequence is known, design is a matter of days. Manufacturing is a cell-free chemical process, easily standardised. Each manufacturing run uses the same facility and equipment; only the RNA sequence changes. This is a fundamental departure from traditional vaccines, which require bespoke cell cultures or egg-based production.
Cancer Vaccines: The Big Prize
The most exciting frontier is personalised cancer vaccines. Unlike a COVID vaccine, which targets a fixed pathogen, a cancer vaccine must target a tumour — and every tumour is genetically distinct. The approach is to sequence a patient’s tumour, identify mutations unique to the cancer, and design an mRNA vaccine encoding those mutant proteins (neoantigens). Administered to the patient, the vaccine trains the immune system to recognise and attack cells carrying those mutations.
Moderna and Merck’s Melanoma Trial
The most advanced program pairs Moderna’s mRNA-4157 (now called V940) with Merck’s immunotherapy Keytruda (pembrolizumab) in patients with high-risk melanoma. In a Phase 2b trial reported in 2023 and updated in 2024, the combination reduced the risk of recurrence or death compared with Keytruda alone, with a meaningful improvement in recurrence-free survival. The result was encouraging enough that a Phase 3 trial has been launched in melanoma and other cancers, including lung cancer.
This is a landmark: a personalised mRNA cancer vaccine showing clinical benefit in a randomised trial. It is not a cure yet, and the effect size is modest, but it validates the concept.
BioNTech’s Pipeline
BioNTech, Moderna’s partner on the COVID vaccine, has built one of the broadest mRNA cancer pipelines. Its autogene cevumeran, a personalised vaccine developed with Genentech, showed promising Phase 1 results in pancreatic cancer — a notoriously deadly disease. In a small trial, patients who mounted a strong T-cell response to the vaccine had substantially better outcomes. BioNTech is also developing fixed, off-the-shelf vaccines targeting shared tumour antigens, including a program in colorectal cancer and a collaboration with the UK’s NHS to deliver personalised vaccines to thousands of patients.
Beyond Cancer: Influenza and Other Diseases
mRNA technology is being applied to influenza, where its flexibility is a major advantage. Traditional flu vaccines are selected months in advance and grown in eggs, which can lead to mismatches if the circulating strain drifts. An mRNA flu vaccine can be updated rapidly. Moderna has reported Phase 3 results for its mRNA flu vaccine, showing it met non-inferiority criteria compared to existing vaccines — not a breakthrough in efficacy, but a validation of the platform’s practicality.
Other targets include RSV (Moderna’s vaccine was approved in 2024, though its uptake has been slower than competitors’), shingles, Epstein-Barr virus, and even HIV, though HIV remains exceptionally difficult because of the virus’s ability to mutate its surface proteins.
Combination and Personalised Medicine
The deeper promise is personalisation. mRNA’s speed means a bespoke therapeutic can be produced for one patient in weeks. Combined with genomic sequencing, this opens the possibility of truly individualised medicine — a vaccine matched to a specific tumour, produced on demand.
The barriers are logistical and economic. Personalised vaccines require tumour sequencing, manufacturing, and quality control on a per-patient basis, with turnaround times measured in weeks. Cold-chain distribution is required. And the cost per patient will be high. Making this work at scale is an operational challenge as much as a scientific one.
Safety and Skepticism
mRNA vaccines have an extensive safety record from billions of doses administered worldwide. Rare side effects, including myocarditis and pericarditis in young males after COVID vaccination, are real and monitored, but the risk of myocarditis from COVID infection itself is higher. Misinformation about mRNA vaccines — including false claims about genome integration and fertility — has been thoroughly refuted but persists, complicating public health efforts.
The Canadian Angle
Canada has been both a consumer and a contributor to mRNA science. BioNTech and Moderna invested in Canadian manufacturing capacity in the wake of the pandemic, and Canadian researchers are involved in cancer vaccine trials. The country’s single-payer health system will face the same question as its peers: how to fund and deliver therapies that can cost hundreds of thousands of dollars per patient.
Adjuvants and the Second Signal
An mRNA vaccine is only half the story. The mRNA carries instructions, but the immune system often needs a second signal — an adjuvant — to mount a strong, lasting response. The lipid nanoparticles that carry the mRNA are themselves mildly inflammatory, which is one reason mRNA vaccines provoke robust immunity. Companies are now engineering better adjuvants and delivery systems to tune the response: stronger against cancer, gentler for routine use, targeted to specific immune pathways. The platform’s modularity helps here too; adjuvants and delivery can be optimised independently of the antigen.
Manufacturing and the Cold Chain
mRNA vaccines have notable logistical advantages — cell-free synthesis, rapid changeover between products, and standardised facilities — but they also have drawbacks. Early formulations required ultra-cold storage, which limited deployment in regions without reliable refrigeration. Improvements have raised stability — some now last months in ordinary refrigeration — but the challenge of distributing to remote or low-resource areas persists. For cancer vaccines, the model is different again: a personalised product for a single patient, manufactured on demand, which tests the industry’s ability to operate a just-in-time, one-off supply chain.
The Cost Question
Personalised cancer vaccines will be expensive. Sequencing a tumour, identifying neoantigens, designing and manufacturing a bespoke vaccine, and doing it within a clinically useful window is a costly, complex process. As with CAR-T therapies, which cost hundreds of thousands of dollars per patient, the price will strain health systems. Whether these therapies become widely accessible depends on manufacturing innovation, economies of scale, and reimbursement decisions by governments and insurers. The technology’s promise is tempered by the economics of bespoke medicine.
Self-Amplifying mRNA and the Next Generation
Researchers are developing self-amplifying mRNA, which instructs cells to copy the RNA instructions themselves, so a much smaller dose is needed. This could reduce cost and side effects. Others are exploring circular RNA, which lasts longer in cells, and mRNA that encodes multiple antigens at once. These advances aim to make the platform cheaper, more durable, and more flexible — critical for the next round of infectious-disease and cancer applications.
Public Trust and the Information Environment
The scientific promise of mRNA runs in parallel with a social challenge: persistent misinformation has eroded confidence in the very technology that could treat cancer. Claims that mRNA vaccines alter DNA (they do not), or affect fertility (they do not), circulate widely despite being thoroughly refuted. For personalised cancer vaccines, where the stakes for individual patients are life and death and where trial recruitment depends on trust, this information environment is a practical obstacle, not a peripheral concern. Rebuilding confidence through transparent communication, independent monitoring, and clinician engagement is as important to the field’s future as any laboratory advance.
The Vaccine Equity Lesson
The COVID-19 experience left a difficult legacy on equity. Despite the speed of development, the distribution of mRNA vaccines was deeply unequal: wealthy countries vaccinated their populations multiple times over while low-income countries waited. The mRNA technology’s promise of rapid, local manufacturing could, in principle, address that — but only if manufacturing capacity and licensing are shared, which has been politically fraught. For the cancer and personalised-medicine applications, the equity question is even starker because of cost. The field’s scientific success will be measured not only in trial results but in whether the therapies reach the people who need them, in the countries where they live. That is a commitment the industry has made repeatedly and delivered on inconsistently.
Conclusion
The COVID experience proved that mRNA can be safe, effective, and rapidly deployable. The next chapter is proving that it can treat cancer, improve on existing vaccines, and enable personalised medicine. The early cancer-vaccine results are genuinely promising — the first randomised evidence that personalised mRNA vaccines benefit patients. The road from promising Phase 2 results to routine clinical use is long and expensive, but for the first time, it looks like a road rather than a wall.
