The scientific team whose 2005 messenger RNA biology discovery at the University of Pennsylvania helped pave the way for Pfizer/BioNTech and Moderna’s COVID-19 vaccines received their first dose of the Pfizer/BioNTech vaccine together on December 18 at Penn, more than 20 years after they began their basic science collaboration.

Drew Weissman, a professor of medicine in Penn’s Perelman School of Medicine, and Katalin Karikó, an adjunct professor at Penn and a senior vice president at BioNTech, together discovered that exchanging one of the four building blocks of messenger ribonucleic acid (mRNA) molecules could greatly increase its therapeutic potential. They shared their perspectives as longtime researchers in the field who are comfortable taking the vaccines themselves, and called on the public to trust the decades of scientific research that has led to these important vaccines now being deployed in the global fight against the virus, encouraging others to get vaccinated when it becomes available to them.

“We understand there are concerns the vaccine was developed quickly, but Kati and I developed our enabling technology fifteen years ago, and we and other scientists have been working on how to use it to develop mRNA ever since,” Dr. Weissman said. “This isn’t brand new—scientists have been studying vaccines using this mRNA platform for at least six or seven years. Based on all of the data available to date, these mRNA vaccines have shown a good safety profile. Clinicians always consider risk–benefit scenarios whenever we recommend a new treatment or a new vaccine to patients and to the public, and with this vaccine there’s no comparison—the benefit is huge and there’s really little to no risk.”

Vaccines relying on mRNA are backed by years of research and safety data, and have several attributes, which are distinct from other historic approaches to vaccine technology. First, they do not contain live virus, so there is no risk of COVID-19 infection from taking the vaccination. Data also show the new vaccines are highly effective, with Moderna and Pfizer/BioNTech clinical trials demonstrating efficacy of about 95 percent in all racial groups. In addition, mRNA vaccines are quicker and easier to produce than traditional vaccines. Other mRNA vaccines are now being studied in clinical trials for HIV, herpes, the Zika virus, rabies, and influenza.

A key element of Drs. Weissman and Karikó’s mRNA discovery is it increases mRNA stability while at the same time decreasing inflammation, further paving the way for these modified mRNAs to be used in a wide array of potential vaccines and treatments. Unmodified mRNA molecules are normally unable to slip past the body’s immune system, but Drs. Weissman and Karikó’s breakthrough research made key changes to the molecular structure and manufacturing of mRNA that allow the resulting modified mRNA to avoid immediate immune detection, remain active longer, and enter into target cells to efficiently instruct them to create antigens or other proteins that fight or treat disease.

“I’m a clinician and a researcher, and ever since I started doing research, my dream was always that I would help develop something that actually benefits people, that goes into people and makes them better, cures their disease, does something to help them,” Dr. Weissman said. “We’re so proud that these vaccines are poised to do that.”

“I feel humbled, and happy,” said Dr. Karikó. “I am more a basic scientist, but I always wanted to do something to help patients. I wasn’t thinking about a vaccine or infectious disease; I was always thinking about developing mRNA for therapeutics. I’m hopeful, now that there is so much interest and excitement for this research, that it will be possible to develop and test this mRNA vaccine technology for prevention and treatment of other diseases, too.”

Beyond COVID-19, the mRNA technologies developed at Penn may lead to new strategies for using mRNA, including development of vaccines targeting other infectious diseases as well as new therapeutics and products for protein replacement, immunotherapy, and personalized cancer vaccines.

Note: The Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines both use licensed University of Pennsylvania technology. As a result of these licensing relationships, Penn, Dr. Weissman and Dr. Karikó have received and may continue to receive significant financial benefits in the future based on the sale of these products. BioNTech provides funding for Dr. Weissman’s research into the development of additional infectious disease vaccines.