Wednesday, December 2

Covid vaccine technology pioneer: ‘I never doubted it would work’ | Sciences


The Hungarian-born biochemist who helped pioneer the research behind the mRNA technology used in the two Covid-19 vaccines that showed positive results, believes it was always a no-brainer.

“I never doubted it would work,” Katalin Karikó told The Guardian. “I had seen the data from animal studies and was looking forward to it. I’ve always wanted to live long enough to see something I’ve worked on approved. “

This month has been the pinnacle of Karikó’s lifelong work researching mRNA, or messenger ribonucleic acid.

The 65-year-old, who left Hungary in 1985 to pursue an academic career in the United States with her husband, a young child and just £ 900 hidden in a teddy bear, has now been suggested as a possible Nobel Prize winner.

His work helped pave the way for the Pfizer / BioNTech and Moderna coronavirus vaccines. Both have been shown to be approximately 95% effective in late stage clinical trials. They are expected to receive emergency approval and deliver to the first patients in the next few weeks.

The key to both is mRNA, a single-stranded messenger molecule that delivers genetic instructions from DNA, coiled within the cell nucleus, to the cell’s protein-making factories outside the nucleus. In the case of vaccines, the molecule signals cells to start producing the harmless spike protein as a warning to the immune system to mobilize against the coronavirus.

The adaptability of mRNA has opened a new field of therapy, not only for vaccines but also for drugs in areas ranging from Cancer stroke and cystic fibrosis.

Karikó joined BioNTech seven years ago, but has struggled to continue her work for the past four decades. He left Hungary, where he had been synthesizing RNA at the University of Szeged, after receiving an invitation from Temple University in Philadelphia. She took her engineer husband and two-year-old daughter with her, along with a teddy bear sewn on to £ 900, the proceeds from the sale of their car, exchanged on the black market.

His daughter, Susan Francia, went on to row for the United States and won two Olympic gold medals in Beijing and London. “She always said that our work ethic was driving her,” Karikó said. The biochemist recalled how one year in May she realized that she had worked every day until then, including New Year’s Day, and occasionally slept in the office as well.

In 1989 she joined the University of Pennsylvania School of Medicine, and it was there that she and her colleagues first saw that mRNA worked. “That’s when I knew it would be something,” he said. But the team collapsed due to lack of funding. “We couldn’t get any money then because it was too new.”

He wanted to use mRNA to treat cystic fibrosis and strokes, but lacked the funds to develop the ideas.

In 1998, Drew Weissman, who was working on an HIV vaccine at the National Institutes of Health, joined the university. “I met him on the Xerox machine and told him that he could make any RNA,” Karikó recalls.

They ended up working together and, in 2005, they made a breakthrough. The problem with the mRNA was that it triggered an inflammatory reaction when injected. The two researchers, however, found a way around this response by modifying one of the four building blocks of mRNA, called nucleosides.

They published their discovery, but it received little attention at the time. Some, including Derrick Rossi, one of Moderna’s founders, now say the duo should receive the Nobel Prize in chemistry for your advancement.

The following year, Karikó and Weissman created a company to develop mRNA drugs, led by Karikó as CEO. But they never got as far as clinical trials, and the university sold the exclusive license to its patent to a third party, CellScript. Meanwhile, Rossi, a Canadian stem cell biologist who had read his groundbreaking 2005 article, found strong financial backers and in 2010 founded Moderna in Cambridge, Massachusetts.

In 2013, Karikó joined BioNTech, he also had a job offer from Moderna, which was based on the Mainz university campus in Germany and at that time did not even have a website.

It’s been a busy seven years. BioNtech now has 1,500 employees and its market value reached a record $ 25 billion (£ 19 million) when the first positive results of trials of the Covid-19 vaccine it has developed with Pfizer were published last week.

Karikó serves as senior vice president of biotechnology and director of RNA protein replacement therapies, and is also an adjunct associate professor at the University of Pennsylvania. Weissman, a professor of medicine at the university, has went on to develop the RNA vaccine candidates against influenza, herpes and HIV.

Both BioNTech and Moderna licensed the modified mRNA technology developed by Karikó and Weissman for their vaccines.

Karikó has high hopes for mRNA as “a universal platform,” for example, as a treatment for epidermolysis bullosa, a serious skin disorder that causes painful blisters. And she already has great ideas about how it might work: “How about we make mRNA that the family can keep in the fridge and apply when their child’s skin peels off?”

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www.theguardian.com

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