Researcher says flu, cancer and malaria and other diseases could be treated with mRNA technology

By Sarah Newey

There are “no limits” to the potential of mRNA technology to treat conditions as varied as cancer, malaria and cystic fibrosis, according to one of the masterminds behind the platform.

In an interview with the Telegraph, Prof Katalin Karikó – a researcher who pioneered the use of mRNA, which was used to develop the highly effective Covid-19 vaccines – insisted researchers are on track to deliver a series of therapeutic breakthroughs via the technology.

This includes personalised cancer vaccines; jabs to combat infectious diseases such as malaria, flu and tuberculosis; and treatments for genetic disorders including cystic fibrosis.

“I am very optimistic [that] for many many things, mRNA will be useful,” Prof Karikó said, speaking from her home in Hungary.

“What is also important is that mRNA can very quickly be made, is very cheap, and it can be individual … there are therapeutic applications, as well as the vaccines,” she added.

Prof Katalin Kariko, a researcher who pioneered the use of mRNA, paving the way for several highly effective Covid-19 vaccines .

Messenger RNA (mRNA) molecules are single-stranded slithers of genetic code formed of nucleosides, which instruct the human cells to produce certain proteins. The idea is that, when you synthesise mRNA code in a lab, you can instruct the body’s defences to better fight a wide range of diseases.

“There are no limits,” Prof Karikó said. “The potential of mRNA, it’s limitless.”

First stop: RSV and flu
The 67-year-old – who relentlessly explored the technology for decades despite demotions, grant rejections and scepticism from fellow scientists – said RSV and influenza vaccines will probably be the first to be approved as, like Sars-Cov-2 shots, they target viruses.

Several candidates are already in development – a phase three trial of Moderna’s mRNA vaccine was launched in February, while Pfizer and BioNTech began a phase 3 trial of their influenza shot in September.

And in November, researchers in the United States announced that an experimental mRNA vaccine provided broad protection against all 20 known influenza A and B virus subtypes in initial tests in mice and ferrets – potentially opening a pathway to a universal flu shot, which could be rolled out in the event of an influenza pandemic.

“[The results imply] the potential for an easily and rapidly constructed universal vaccine that could be of great use in the event of a pandemic outbreak of a novel influenza virus,” said Prof Estanislao Nistal, a the CEU San Pablo University in Madrid.

‘Paradigm shift’ for cancer
Significant progress has also been made in the race to develop cancer treatments. Last week, Moderna and Merck announced promising results for their phase 2b trial of a personalised mRNA skin cancer vaccine, which is designed to prime the immune system so the body can generate a response to a specific cancer tumour.

When combined with the drug Keytruda, the jab led to a 44 per cent reduction in the risk of the cancer returning in patients who had seen their tumours removed, compared with the single use of Keytruda in patients with stage three and four melanoma.

Moderna’s Chief Medical Officer, Paul Burton, said the development was a “paradigm shift”. Prof Karikó added that the trial demonstrates the approach is “successful”, though further innovations are still needed as results do not show that the vaccine can treat “huge tumours”.

“It shows that if a small number of tumour cells survive [after an operation], you can eliminate them with an mRNA vaccine combined with [other drugs]. It shows this is a success, a powerful combination, and offers direction for further research,” she added.

Many other companies – including BioNTech, where Prof Karikó was a a senior vice president until earlier this year – are also working on “exciting” potential mRNA cancer vaccines, she added.

‘Burning issues’: malaria and cystic fibrosis
But for now, Prof Karikó is most excited about work in two other areas: malaria vaccines, and cystic fibrosis treatments.

“Malaria, it’s something where so many people have tried so many things,” she said. For decades, scientists have struggled to develop shots to target the mosquito-borne parasitic diseases – and while the first vaccine was finally approved last year, efficacy is not as high as the World Health Organization would like.

In July, BioNTech announced that it planned to start clinical trials for its mRNA malaria vaccine within the next six months – and Prof Karikó said she is optimistic after the results in animal studies. The challenge, however, is not developing the vaccine itself, but ensuring that mRNA is primed to target the right part of the malaria parasite.

“For parasites like malaria, the pathogen is much bigger [than a virus]. So it is more difficult to figure out what the mRNA code is that would generate a very effective immune response,” she said. “So these processes are ongoing … but it is a very meaningful goal. Malaria is a major threat, a burning issue … and the medical need is clearly there.”

Work on cystic fibrosis is further behind, Prof Karikó said – and the first experimental mRNA treatment, from Translate Bio, failed to improve lung function in patients with the genetic disorder last year. But is an area she’s especially interested in, having worked on the condition in the early 1990s, and she insists several approaches are in the pipeline.

“I am excited … I believe that it will be successful,” she said. “There is a major role for mRNA in targeting genetic diseases … [but] there is some way to go.”

Yet, for now – 44 years after she first began work on mRNA at a lab in Hungary – Prof Karikó has taken a small step back from the frontlines of mRNA research. While she is still working as a consultant on projects to make mRNA more potent, she left her permanent position at BioNTech earlier this year.

Since the company’s Covid-19 vaccine proved effective, life has been a chaotic jumble of jumping between continents – Prof Karikó has received a string of honorary degrees and awards, including from Semmelweis University in Budapest last week, and believes she has a responsibility to educate the public and inspire the next generation of scientists.

“One lesson [of the pandemic] was that we need to educate the public… For years, we thought ‘science, of it’s too complex’. But now people are talking about PCR tests, about mRNA – we have to trust the public is able to learn, and combat misinformation. During the pandemic it was too little, too late, when we hadn’t done it all along.

“I do not crave recognition, because from my perspective, all the work was fun,” she added. “I see a role to advertise science, to talk to the press … and to help encourage young ones and women to go into sciences.”
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Credit: The Telegraph