The Frontiers of Knowledge award honors the fathers of messenger RNA vaccines, whom nobody believed in the beginning

Research on messenger RNA (mRNA), which has allowed the development of vaccines against covid, was recognized this Wednesday by the BBVA Frontiers of Knowledge Foundation by awarding its highest annual award in Biology and Biomedicine (endowed with 400,000 euros) to Katalin Kariko, Robert Langer, and Drew Weissman. The three scientists, according to the jury, have been awarded "for their contributions to messenger RNA therapies and for the transfer technology that allows our own cells to produce proteins for the prevention and treatment of diseases." The Hungarian Karikó, whose first investigations were rejected until she lost her position at the university, and the American Weissman, who suffered similar problems, were distinguished last year with the Princess of Asturias awards. Langer,also from the US and a researcher at the Massachusetts Institute of Technology (MIT), recalled that his work was rejected up to nine times before being taken into account.

The works of the biochemist Karikó, daughter of a Hungarian butcher; Weissman, the immunologist with whom he has collaborated for 20 years; and chemical engineer Langer have allowed the creation of Moderna and Pfizer-BioNTech vaccines, based on messenger RNA (instructions for the generation of a protein that triggers the immune response). After half a century of struggle in this field, despised in its beginnings, his research has been essential for the creation of vaccines in a time 10 times less than usual for this type of drug.

Langer, who specializes in drug delivery systems and tissue engineering, is on Moderna's board. This MIT professor was the first to point the way to research when, in the 1970s, he showed that it was possible to encapsulate nucleic acid molecules in nanoparticles and transfer them inside the body. According to the jury, “it thus opened the door to packaging therapeutic macromolecules, including mRNA, in such a way that they can be transferred to cells and that the cellular translation machinery itself synthesizes the antigenic protein”.

Karikó, now part of Pfizer, studied the possibilities of modifying the genetic molecule called messenger RNA to instruct human cells to produce personalized proteins.

His initial idea was to develop therapies for heart disease, but the coronavirus overturned his goals to focus on solving the pandemic.

The American immunologist Drew Weissman, who forms part of Karikó's team together with Norbert Pardi, from the University of Philadelphia, was responsible for creating the appropriate package for the messenger RNA to reach the muscle cells of the arm and those of the immune system .

Karikó and Weissman, both professors at the University of Pennsylvania (USA), developed methods of modifying mRNA to prevent its destruction by the human immune system.

In early work they found that RNA given to lab mice sometimes caused harmful inflammation.

According to Óscar Marín, director of the Center for Neurodevelopmental Disorders at King's College London (United Kingdom) and secretary of the jury, “the contribution was a key advance”.

Marín explains that “Karikó and Weissman discovered how to modify mRNA molecules to make them capable of being used as a therapeutic agent and Langer devised the safe vehicle, the encapsulation technology that allows mRNA to be introduced into the body.

The two advances are essential”.

The jury has recognized their advances in a technique that goes beyond the accelerated development of injections that prevent the severity of covid: “The vaccines that are containing the pandemic are only the beginning of a technology called to be extended to other therapeutic areas , such as autoimmune diseases, cancer, neurodegenerative disorders, enzyme deficiencies and other viral infections”.

And adds Óscar Marín: “This award recognizes the creators of the two technologies that, together, have not only made vaccines against covid possible, but also open up a whole range of therapeutic possibilities in very diverse areas for the future.

Vaccines have been the first example of the potential of the union of these two technologies, but research is already under way and there are clinical trials on their use against other diseases”.

a complicated path

The road has not been easy.

Katalin Karikó, born in the Hungarian town of Szeged 67 years ago, suffered initial rejection in her research and ran out of public funds in 1995 (10 years after emigrating to the US), for which she lost her position as head of University.

However, he continued his efforts with cardiologist Elliot Barnathan and later with neurosurgeon David Langer.

After learning of the jury's decision, according to the BBVA Foundation, Katalin Karikó explained: "For 40 years, not only did I not receive any prize, but I did not receive any financial support for my research, so this recognition is a great honor." . I want to take advantage of the fact that I am under the spotlight of the media to encourage young people to dedicate themselves to science, because it is exciting”.

Weissman, born in Lexington (Massachusetts) 63 years ago, has also recalled the initial difficulties in some findings that have ended up saving millions of lives: "Our central hypothesis when we started this work was that RNA would be a better system for transferring proteins to the body , because it would turn the receiving body itself into the factory that produces the therapy.

The problem we ran into is that RNA was highly inflammatory, and the animal we injected it into would get sick, so Katalin and I spent many years trying to figure out the cause of this problem, and that's how we got our main finding: a method to avoid the inflammatory reaction of RNA.

This also had the effect of increasing the amount of protein being produced, which was a huge added bonus."

Langer, the oldest of the three researchers (born in Albany, New York, 74 years ago) and also awarded the Prince of Asturias Award in 2008, has faced the same skepticism about his research for decades: “Before in 1974 managed to create micro and nanoparticles to encapsulate large molecules, people did not believe it was possible.

Even after the result was published, many people told me that it was wrong, they didn't believe it.

The first nine research projects I applied for were rejected and I couldn't get a job in a chemical engineering department, which is my discipline."

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