Behind the Scenes in the Lab and the Future of mRNA Research

It’s fair to call Drew Weissman, MD, PhD, the Roberts Family Professor for Vaccine Research in Penn’s Perelman School of Medicine, and Katalin Karikό, PhD, an adjunct professor in Neurosurgery, household names in the science world. After their revolutionary mRNA research gave way to a safe and highly effective vaccine platform and the mRNA COVID-19 vaccines, next came recognitions. From receiving the highly-prestigious Lasker Award to being named Time Magazine People of the Year, the two are now no strangers to the spotlight. But the story of mRNA research has a large cast of characters, especially when looking ahead to what the future holds for the power mRNA research.

“When I am asked who I am grateful for and who I have to thank for all the successes I’ve had in my research work, besides Kati [Karikó], I always think of the members of my lab,” said Weissman. “The scientists and students in my lab are continuing to help us build further understanding of mRNA vaccines and create mRNA vaccines for a variety of infectious diseases. I have a very determined, smart, and passionate team.”

Many individuals tied to Weissman and his lab have, over the years following their training and work at Penn, gone on to their own labs, to different universities, institutions, biomedical companies, and careers. Today, the lab is made up of 29 people. They’re a melting pot of genders, ages, and ethnicities, united by an unyielding drive and a belief in mRNA technology. Here are just a few of the scientists from and around the Weissman Lab, who are advancing mRNA research at Penn today.

Elena Atochina-Vasserman, MD, PhD

Some of Atochina-Vasserman’s first memories of growing up in the Soviet Union revolve around looking at the lungs.

“My dad was a pulmonary radiologist in Siberia, and I remember looking at X-ray images hung on the light board in our home,” said Vasserman, an adjunct assistant professor of Infectious Diseases. “I’d ask him questions, and he’d point out dark and light areas of the lungs and explain details of lungs where there was damage or inflammation. Since the very beginning, I’ve thought about lungs.”

Atochina-Vasserman received her medical doctorate and PhD in Russia, studying drug delivery to the lungs. She then got an opportunity to join Penn as postdoctoral researcher in 1992.

“I called my Dad when I heard the news, and he was so proud that I was going to America, he almost cried,” she said. The moment would prove bittersweet: He unfortunately passed away unexpectedly only five days later.

At Penn, Vasserman worked under the supervision of Vladimir Muzykantov, PhD, in the lab of Aron B. Fisher, MD, at the Institute for Environmental Medicine and from 1997 with Michael F. Beers, MD, as a research associate and then became a senior research investigator in the Pulmonary, Allergy, and Critical Care Division. In 2018, she joined the Weissman lab to continue to develop new technologies for drug delivery to the lungs. She also leads the project on the development of an mRNA norovirus vaccine. Both of these employ mRNA and lipid nanoparticles which encase the mRNA and allow it to reach and activate the immune system appropriately.

“Four component lipid nanoparticles do not work well as a delivery system to the lungs, and therapeutics need to reach a lower portion of the lung in order to treat acute lung injury or diseases like pulmonary fibrosis,” said Atochina-Vasserman. “In collaboration with Dr. Virgil Percec, PhD, we have developed a new one-component lipid delivery system that delivered mRNA to the respiratory portion of the lung with high efficiency. And, apart from my pulmonary work, I’m leading our research on development of an mRNA norovirus vaccine. We have great pre-clinical data, and we hope to test it in clinical trials very soon.”

When walking around Weissman’ s lab, you’ll likely see Atochina-Vasserman leading her colleagues: walking around, mentoring young investigators and interns, and generally keeping all activity in the lab running smoothly, purposefully, and efficiently.

“I love to share my knowledge and work with young scientists,” Atochina-Vasserman said. “I try to tell them there are a lot of failures before success. You have to really love it.”

Norbert Pardi, PhD

Pardi’s story is reminiscent of another mRNA researcher’s journey: Karikó’s own. Also from Hungary, Pardi came from the same small town of Kisújszállás. After pursuing a graduate degree in Hungary, he reached out to Karikό for career advice.

“Our families knew each other for a long time because my grandfather and Katalin’s father worked in the same butcher shop,” said Pardi, an assistant professor of Microbiology. “We had so many similarities, and those just increased when I started mRNA research.”

Karikό connected Pardi with Weissman, and the two eventually encouraged Pardi to come to Philadelphia and join the Weissman lab. He’s been at Penn since 2011 and now has his own lab at Penn in the department of Microbiology.

Pardi has been developing a universal mRNA flu vaccine — meaning the vaccine would protect against multiple influenza virus strains.

“Influenza viruses mutate very quickly,” said Pardi. “Vaccine developers have to use information available at the time regarding the prevalence of different flu strains and then basically guess what strains are going to be around later that year. This leads to flu vaccines that are often very inaccurate and offer sub-par protection against the flu.”

Pardi believes that mRNA vaccines can be designed to target several proteins of various types of flus and therefore protect against virtually any strain. He expects that there will be clinical trials for his universal influenza vaccine in the next couple years.

“The mRNA vaccines can also be made to stimulate the production of many different antigens instead of just one which can also allow for greater protection with just one vaccine.”

Matthew Pine

Doctoral candidate Matthew Pine has long been passionate about medicine and having a career that helped people — picking up the torch from his grandfather who was a co-inventor of the antibiotic tetracycline. It was in college when he first started working on mRNA vaccines with Merck.

After graduating in 2018, Pine began a PhD program at Penn, and not long after, he heard Drew Weissman speak for the first time. “Drew came to one of my biology classes and spoke about his mRNA vaccine platform,” recalled Pine. “People were like, ‘what kind of magic trick is this?’ I remember thinking, ‘It worked well in my previous experiments with Merck. I think this guy is on to something.’”

Subsequently, Pine joined the Weissman Lab with Weissman and Pardi serving as his mentors. Since then, he has participated in dozens of experiments, many focusing on a preventive vaccine for Lyme disease.

“Annual cases of the virus have gone up by roughly 200,000 compared to figures when I began my research,” said Pine. “It’s a disease that can be difficult to diagnose and that can have very dangerous consequences if left untreated.”

Since his time in the Weissman Lab, Pine says what he has learned most from Weissman and Pardi is the value of humility.

“These are two people who are not only very smart, but they also do not flaunt it. They are are just good people that genuinely want to help humanity,” said Pine. “I think the most important characteristic for a scientist is, above all else, remaining grounded and treating fellow lab members and collaborators with kindness and respect.”

Nathan Ona

A New York native with nurses for parents and 2022 graduate of Drexel University with a bachelor’s degree in biomedical science and engineering, Ona joined the Weissman lab as a student through Drexel’s Cooperative Education Program in November 2020 and supported Atochina-Vasserman and her research. Just weeks ago, he was hired full-time as a research assistant, largely to focus on one-component lipid nanoparticle as a delivery mechanism for mRNA.

“I had experience with a medical device company developing software but really was hungry for lab and biochemistry research experience,” said Ona. “I was fortunate enough to join the Weissman Lab during the pandemic, a time when mRNA vaccines were just being appreciated worldwide and beginning to literally save lives. It was thrilling but a place where I have really been able to learn and develop my skills and understanding of mRNA.”

Ona said he’s found a passion through this work and is particularly interested in further exploring mRNA delivery methods, research he has done under the supervision of Atochina-Vasserman. He plans to pursue graduate school in the future.

“Engineering and software development, like medical research, exist in ‘what ifs,’” said Ona. “You are creating something to behave a certain way, and in turn, solve a problem. I think we are just beginning to uncover all the things we can do with mRNA, and this work feels important.”