COVID-19 mRNA Vaccine Pioneers

After a brief exchange over who could use the copier next, Drs. Karikó and Weissman struck up a conversation. He said he was using DNA to make an HIV vaccine. She argued for RNA. Intrigued, he asked her to join his lab.

Dr. Karikó was an expert in RNA but not a physician with immunology expertise. Dr. Weissman was a practicing immunologist but didn't have Dr. Karikó's RNA experience. Their combined backgrounds created a perfect environment for shared understanding and research.

We shared knowledge. We shared papers. We taught each other everything. But by doing that, it allowed us to figure out how to make modified RNA and how to make this vaccine. And I think either of us alone, that would have never happened because we needed both elements, both types of science involved.

In petri dish experiments, Dr. Karikó’s modified mRNA molecules could instruct cells to make the protein she desired. Her goal was the same when injecting mRNA into mice: New genetic instructions would cause the mice to make a customized protein and elicit an immune response. Unfortunately, the mice experienced harmful inflammation, and some died.

After several more experiments Drs. Karikó and Weissman made a breakthrough. They found that modifying part of the mRNA eliminated inflammation. Also, encapsulating the mRNA in tiny lipid (fat) droplets created molecules that, instead of being cast out by the immune system, worked with it to fight disease.

We kept doing experiments. We kept getting results. We kept getting excited by the results.

In 2005, Drs. Karikó and Weissman published landmark research that explained how mRNA could be altered for therapeutic use. They also revealed how mRNA can be delivered into the body to reach the proper target. Unfortunately, few scientists paid attention. Undeterred, Drs. Karikó and Weissman persevered.

Then COVID-19 hit, and the modified mRNA technology developed at Penn Medicine by Drs. Karikó and Weissman took center stage. Both Pfizer/BioNTech and Moderna licensed Penn technology, which is used in the vaccines now being deployed to combat the virus.

The Pfizer/BioNTech vaccine was the first to receive FDA Emergency Use Authorization (EUA) in December 2020 for those 16 or older, and the first COVID-19 vaccine to receive full vaccine approval for the same age group. In May 2021, the EUA was expanded to include adolescents ages 12 to 15. In August 2021 it was amended again to allow for a third dose for certain people who are immunocompromised. The vaccine remains available under EUA for these groups. Moderna Therapeutics, which was granted EUA for its mRNA COVID-19 vaccine in December 2020, also uses the same modified mRNA technology created at Penn.

To date, a combined 360 million doses of mRNA COVID-19 vaccine have been administered in the U.S. alone. The Pfizer/BioNTech vaccine is protecting people from the disease in 126 countries across the globe, and 71 countries are using the Moderna vaccine.

On December 18, 2020, Drs. Karikó and Weissman received their first doses of the Pfizer/BioNTech COVID-19 mRNA vaccine, more than 20 years after meeting at that copy machine.

Beyond COVID-19, the potential for using modified mRNA to prevent and heal disease are extensive. Read this Q&A with Dr. Weissman about the COVID-19 vaccine and mRNA technology's future applications.

The work of Drs. Weissman and Karikó is the scientific foundation on which these innovative and lifesaving vaccines rest. Their discovery of how to chemically modify mRNA to more effectively produce proteins in vivo laid the groundwork for the rapid development and deployment of mRNA vaccines—and has sparked a completely new way to look at prevention of infectious diseases and novel pathways for the treatment of cancer and other serious conditions.