Messenger RNA: How a remote idea led to COVID-19 vaccines

WASHINGTON – Hungarian-born scientist Katalin Kariko’s obsession with researching a substance called mRNA to fight disease once cost her a faculty position at a prestigious U.S. university, which dismissed the idea as a dead end.

Now, his pioneering work, which paved the way for the Pfizer and Moderna COVID-19 vaccines, could be what saves the world from a 100-year pandemic.

“This is just unbelievable,” she told AFP in a video call from her home in Philadelphia, adding that she was not used to the attention after years of working in the dark.

It shows why “it is important that science should be supported on many levels.”

Kariko, 65, spent much of the 1990s writing grant applications to fund her research on “messenger ribonucleic acid,” genetic molecules that tell cells which proteins to make, essential for keeping our bodies alive and healthy. .

She believed that mRNA was the key to treating diseases where having more of the right kind of protein can help, such as repairing the brain after a stroke.

But the University of Pennsylvania, where Kariko was on her way to obtaining a professorship, decided to disengage after grant rejections mounted.

“I was ready for a promotion, and then they demoted me and expected me to walk out the door,” she said.

Kariko still did not have a green card and needed a job to renew her visa. He also knew that he couldn’t send his daughter to college without the considerable staff discount.

She decided to persist as a lower-level researcher, getting by on a meager salary.

It was a low point in his life and career, but “I thought … you know, the (lab) bench is here, I just have to do better experiments,” he said.

The experience shaped his philosophy for dealing with adversity in all aspects of life.

“Think hard and then at the end, you have to say ‘What can I do?’

“Because then you don’t waste your life.”

The determination runs in the family: Her daughter Susan Francia went to Penn, where she earned a master’s degree and won gold medals with the US Olympic rowing team in 2008 and 2012.

– Twin Advances –

Inside the body, mRNA delivers to cells the instructions stored in DNA, the molecules that carry our entire genetic code.

In the late 1980s, much of the scientific community focused on the use of DNA to deliver gene therapy, but Kariko believed that mRNA was also promising, as most diseases are not inherited and do not need solutions. that permanently alter our genetics.

However, it first had to overcome a major problem: In animal experiments, synthetic mRNA was causing a massive inflammatory response when the immune system detected an invader and scrambled to fight it.

Kariko, along with her senior collaborator Drew Weissman, discovered that one of the four building blocks of synthetic mRNA was failing, and they were able to overcome the problem by swapping it out for a modified version.

They published an article on the breakthrough in 2005. Then, in 2015, they found a new way to deliver mRNA to mice, using a fatty layer called “lipid nanoparticles” that prevent the mRNA from degrading and help place it into the correct part. of cells.

Both innovations were key for the Covid-19 vaccines developed by Pfizer and its German partner BioNTech, where Kariko is now senior vice president, as well as for the injections produced by Moderna.

Both work by giving human cells the instructions to produce a coronavirus surface protein, which simulates an infection and trains the immune system for when it encounters the real virus.

– New treatments –

The mRNA degrades rapidly and the instructions it gives the body are not permanent, making the technology an ideal platform for a variety of applications, Kariko said.

These could range from new flu vaccines, faster to develop and more effective than the current generation, to new treatments for diseases.

For example, AstraZeneca is currently working on an mRNA treatment for patients with heart failure, which provides signaling proteins that stimulate the production of new blood vessels.

Although she doesn’t want to make it too much of a deal, as a foreign-born woman in a male-dominated field, she occasionally felt underrated, saying that people would come up after lectures and ask “Who is your supervisor?”

“They were always thinking, ‘That woman with an accent, there must be someone behind her who’s smarter or something,’” he said.

Now, if all goes well with the Pfizer and Moderna vaccines, it’s not hard to imagine the Nobel Prize committee rewarding Kariko and her fellow mRNA researchers.

That would be bittersweet for Kariko, whose late mother called her every year after the ads to ask why she hadn’t been chosen.

“‘I never get (federal) grants in my life, I’m nobody, not even a college,'” he laughed. To which his mother replied, “But you work so hard!”

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