How mRNA went from a scientific backwater to a pandemic crusher

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In 1995, Katalin Karikó was at her lowest ebb. A biochemist at the University of Pennsylvania (UPenn), Karikó had dedicated much of the previous two decades to finding a way to turn one of the most fundamental building blocks of life, mRNA, into a whole new category of therapeutics.

More often than not, Karikó found herself hitting dead ends. Numerous grant applications were rejected, and an attempt to raise funding from venture capitalists in New York to form a spin-off company had proved to be a fruitless endeavour. ”They initially promised to give us money, but then they never returned my phone calls,” she says.

By the mid 1990s, Karikó’s bosses at UPenn had run out of patience. Frustrated with the lack of funding she was generating for her research, they offered the scientist a bleak choice: leave or be demoted. It was a demeaning prospect for someone who had once been on the path to a full professorship. For Karikó’s dreams of using mRNA to create new vaccines and drugs for many chronic illnesses, it seemed to be the end of the road.

Thirty four years earlier, the discovery of mRNA had been announced amidst a clamour of scientific excitement in the summer of 1961. For more than a decade, researchers in the US and Europe had been attempting to unravel exactly how DNA is involved in the creation of proteins – the long strings of amino acids that are vital to the growth and functioning of all life forms.

It transpired that mRNA was the answer. These molecules act like digital tape recorders, repeatedly copying instructions from DNA in the cell nucleus, and carrying them to protein-making structures called ribosomes. Without this key role, DNA would be nothing but a useless string of chemicals, and so some have dubbed mRNA the ‘software of life.’

At the time the nine scientists credited with discovering mRNA were purely interested in solving a basic biological mystery, but by the 1970s the scientific world had begun to wonder if it could exploit this cellular messaging system to turn our bodies into medicine-making factories.

Artificial mRNA, designed and created in a petri dish and then delivered to the cells of sick patients through tiny packages called nanoparticles, offered a way of instructing the body to heal itself. Research groups around the world began looking into whether mRNA could be used to create the vaccines of the future by delivering messages to cells, teaching them to create specific antibodies to fight off a viral infection. Others started investigating whether mRNA could help the immune system recognise and destroy cancerous tissue.

Karikó was first exposed to these ideas as an undergraduate student in 1976, during a lecture at the University of Szeged in her native Hungary. Intrigued, she began a PhD,…



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