The jury of the BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine has selected Katalin Karikó, Robert Langer and Drew Weissman for their contributions to messenger RNA therapeutics and the technology that enables our own cells to produce proteins for the prevention and treatment of disease. The first clinical application of their work was the development of vaccines against SARS-CoV-2.
Karikó and Weissman, biochemist and immunologist respectively, discovered how to modify messenger RNA (mRNA) molecules so that they could be used as a therapeutic agent, while chemical engineer Robert Langer devised the technique of nanoparticle encapsulation that allows mRNA to be introduced into the body.
Messenger RNA-based vaccines are produced faster than traditional vaccines and can more easily adapt to virus mutations. They are also theoretically safer vaccines, since no live virus is involved in the process, and no genetic material enters the nucleus of the human cell.
“This award recognizes the inventors of two technologies that, together, have not only given us vaccines against COVID-19, but also open up a whole vista of therapeutic possibilities in the most widely diverse areas for the future. Vaccines are the first example of the potential of bringing these two technologies together, but further research and clinical trials on their use against other diseases are already underway,” explains Óscar Marín, Director of the Centre for Neurodevelopmental Disorders at King’s College London (United Kingdom) and Committee Secretary.
Katalin Karikó. BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine.
A technology that teaches the body to “manufacture” its own treatment
The three laureates are the authors of critical breakthroughs in the chain of scientific findings that have made messenger RNA therapies a reality, with a technology that gets the body’s own cells to produce the molecules needed to fight off disease.
“Karikó and Weissman discovered how to modify mRNA molecules to make them suitable as a therapeutic agent, and Langer came up with the vehicle, the encapsulation technology that enabled the mRNA to be delivered into the body,” explains Marín. “They are both quintessential advances.”
Timewise, the first contribution came from Robert Langer, a professor at the Massachusetts Institute of Technology (USA). In the 1970s, Langer published in the journal Nature the first work demonstrating that it was possible to encapsulate nucleic acid molecules - such as ribonucleic acid (RNA) - in nanoparticles and transfer them into the body. It opened the door to the “packaging of macromolecule therapeutics including mRNA and delivering them into cells, allowing the cellular translation machinery to synthesize the protein/antigen,” explained the committee.
The contribution of Karikó and Weissman, both professors at the University of Pennsylvania (USA), came well into the new century. In the words of the award citation, “together they developed mRNA modification methods to prevent its destruction by the human immune system,” once inside the organism.
40 years of research without financial support
After learning of the jury's decision for these awards, which have become the prelude to the Nobel Prize, Katalin Karikó explained how she feels now that the success of vaccines has placed her work at the center of science: “For 40 years, not only did I not receive any award, but I did not receive any financial support for my research, so this recognition is a great honor. I want to take advantage of being in the media spotlight to encourage young people to dedicate themselves to science, because it is exciting.”
Robert Langer. BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine.
Langer also faced the same skepticism as Karikó decades earlier. Before succeeding in creating micro- and nanoparticles to encapsulate large molecules in 1974, “people didn't believe it was possible,” he recalled after learning of the jury's decision. “Even after the result was published many people told me it was wrong; they didn't believe it. The first nine grants I applied for were rejected, and I couldn’t get a job in a chemical engineering department, which is my discipline.”
Langer would eventually join MIT as a Professor of Nutritional Biochemistry in 1978 and is today one of the world's most cited scientists, author of more than a thousand patents, and co-founder of the company Moderna.
His technology has been “absolutely critical” for mRNA therapies. “If you injected mRNA directly, it would just get destroyed. But you put it in these little particles and that protects it when you inject it into the body, and allows it to survive and do its work,” he explains.
The dawn of a biomedical revolution
Karikó began working with synthetic RNA in the late 1970s at the Szeged Biological Research Center in his native Hungary. In 1985 he emigrated with his family to the United States. The turning point of his career was the beginning of a collaboration with immunologist Drew Weissman at the same university. In 2005 Karikó and Weissman achieved their first breakthrough: discovering how to modify RNA in such a way that the human immune system cannot detect it.
Drew Weismann. BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine
The initial goal of their research, however, was not to develop a vaccine, Karikó explained. “My goal was to use mRNA to encode a therapeutic protein that could be administered to a patient with a stroke or myocardial infarction because I worked in the field of cardiology and neurosurgery, and I wanted to prevent inflammation that could worsen the patient's situation.”
For the award winner, the COVID-19 vaccines are just the beginning of a biomedical revolution in the making. “Now that the technique has proved its usefulness in vaccine development, I am sure we will soon see new versions for other diseases. It is also a very cheap therapy, because the medicine is made in your own body; you are the factory. The applications are endless.”
Karikó noted that there are already advanced phase clinical trials of this technique against cardiovascular diseases, “injecting mRNA into the heart during bypass surgery to increase cardiac capacity.” Trials are also underway to test mRNA vaccines against HIV, malaria and other diseases, including cancer, as Karikó points out: “We have conducted promising trials in two animal models to combat multiple sclerosis, an autoimmune condition. A lot of trials have begun, and more and more firms are trying out the technology.”
Meanwhile, Weissman also highlights his current work on the possible development of “gene therapies for sickle cell anemia, a disorder with which 200,000 people are born each year. We hope to treat them with a single injection of mRNA that will target the bone marrow stem cells, and fix their genetic disorder, curing the disease. This would change medicine.”