Katalin Kariko spent years and years focusing on the messenger RNA. Her applications for grants were rejected numerous times, but she eventually became recognized in 2020. Kariko’s work turned out to be perfect for the synthesis of the Pfizer/BioNTech Covid-19 vaccine. Now it may help save us from a global pandemic.
Katalin Kariko’s dismissed idea
In the 1990s, Kariko was up a professorship at the University of Pennsylvania. She wanted to investigate mRNA- messenger RNA, which directs the synthesis of protein in our cells. She thought it could help treat diseases in which protein synthesis was crucial, and she was very optimistic it would work. However, the world didn’t share her enthusiasm, and the rejections of the grant applications were piling up. Eventually, the university demoted her, and she decided to continue low-rung research. Despite that, she decided to push through with her work. “Think through, and then at the end of it, you have to say ‘What can I do?’. Because then you don’t waste your life.” she told AFP on a video call.
Being a woman in a male-dominated field and an immigrant, Kariko wasn’t always respected. “They were always thinking, ‘That woman with the accent, there must be somebody behind her who is smarter or something,'” she explains, pointing out how people would ask her who is her supervisor after she delivered a lecture. With the massive success of the mRNA vaccines, it is pretty evident that Katalin Kariko is a frontrunner for the Nobel Prize. After years of effort, she finally got the recognition she deserved.
The Study of mRNA
What is mRNA?
mRNA is a genetic molecule synthesized in our bodies from DNA during a process we call transcription. Afterward, it contains information from our genetic code (from DNA), and it directs the cell which proteins to make during a translation process. Whereas gene therapy using DNA permanently alters the genetic code, mRNA doesn’t stay in the organism for too long.
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Overcoming issues with mRNA
The first issue Kaiko had to overcome to make using mRNA possible was the inflammatory response to mRNA injections during animal testing. The immune system recognized the synthetic mRNA as hostile and therefore tried to eliminate it, causing inflammation. Katalin Kariko collaborated with David Weissman, an immunologist with a Ph.D. from Boston University, and after a decade of testing, they resolved the issue. They discovered that synthetic mRNA had a defect within its building blocks. When one of the blocks was replaced with a modified version, the inflammation didn’t occur. Kaiko and Weissman published papers on their discovery in 2005, and only a few people saw its potential.
The second breakthrough
However, that was not the end of struggles with mRNA. After its injection into the organism, it needed protection from degradation and directions to a specific part of the cell. Ten years later, Katalin Kariko and David Weissman discovered how to kill birds with one stone. Using “lipid nanoparticles” as a form of fatty coating prevented mRNA degradation and helped with its correct placement. Both breakthroughs were vital for the synthesis of the Covid-19 vaccine five years later.
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The Covid-19 vaccine
“The mRNA quickly degrades, and the instructions it gives the body aren’t permanent, making the technology an ideal platform for a variety of applications,” explains Kariko. The technology saves gene therapy from the controversy of permanently altering a human genome.
The mRNA vaccine works with a simple mechanism. The classic vaccine consists of a dead or weakened pathogen, enabling the immune system to practice fighting it. Therefore, it grants immunity to the illness or makes treating it faster and less dangerous for the patient. However, the mRNA vaccine doesn’t contain a pathogen at all.
Instead, it has an mRNA piece that instructs cells to create a surface protein of a specific pathogen or another kind of signal molecule. It generates a simulated infection and provides an immune system solid training for encountering the actual pathogen. That means, instead of letting the burglar in, the mRNA vaccine allows sending out a wanted notice. When the pathogen enters the organism, its immune system already knows everything it needs to fight it.
The Pfizer/BioNTech vaccine and the Moderna vaccine are mRNA vaccines. Katalin Kariko spent years doing underfunded research that not many believed in, now she became a senior vice president at BioNTech, and the mRNA became a million-dollar idea. Astra Zeneca is working on mRNA delivering signals that stimulate the synthesis of blood vessels, which would be a new treatment for heart failure patients. This would have never been possible without Katalin Kariko’s determination and persistent work over the years.