The Nobel Assembly on Monday awarded the 2023 Nobel Prize in Medicine to Hungarian-American biochemist Katalin Karik? and immunologist Drew Weissman for their pioneering work on mRNA vaccines. Their research has been instrumental in the fight against COVID-19, enabling the development of vaccines within months of the virus striking the world. The scientists figured out how to deliver gene-editing mRNA to the target cells inside a protective nanoparticle and how to trigger a robust immune response to evade the host’s natural defenses. Their approach is now crucial to the global effort to contain the coronavirus outbreak. It may lead to a new generation of vaccines against other infectious diseases and cancer.
Weissman and Kariko, studying protein structures at the University of Pennsylvania, began their careers studying how cells control genes. In the 1990s, they realized that mRNA, a messenger version of the DNA that encodes instructions for building proteins in the body, could be used to convey genetic information to the target cell. But mRNA was unstable and would quickly degrade before it got to the cell where it was needed. They solved this problem by replacing one of the uridine nucleotides in the mRNA molecule with an analog that looked and worked the same but did not trigger an immune response. The resulting molecule, which they called “siRNA,” was stable and could successfully slip into the target cell, where it directed the synthesis of the protein it encoded.
They also developed a way to package siRNA in lipid nanoparticles that protected the molecule and kept it stable until it reached its destination inside the cell. They did not know it then, but their fundamental discoveries were vital to overcoming the inertia that stalled previous efforts to develop mRNA-based vaccines. Their work inspired the creation of two companies that made mRNA-based vaccines for the pandemic, Moderna and BioNTech.
The vaccines these firms developed were effective against the novel virus that struck the world, but they are safe and effective in clinical trials and have now reached millions of people worldwide. “The mRNA vaccines were a game-changer for this pandemic,” said Dr. Paul Hunter, a professor of medicine at Britain’s University of East Anglia, who has studied the impact of the vaccines on the human body and is among those who credit them with halting the spread of the virus and reducing deaths from it.
The mRNA vaccines were quick to develop and get into the hands of physicians, but their success is not without controversy. Some skeptics of the technology have argued that it is not as simple as delivering a synthetic protein to the immune system and letting the host’s immune system do its work. Others have criticized the rapid rollout of the vaccines, which some say was not thoroughly tested. Peter Maybarduk, a vaccine expert at the Washington advocacy group Public Citizen, welcomed the Nobel Prize recognition but warned that the honor should be “deeply embarrassing” for Western countries for not vaccinating their populations against the virus sooner.