Technology & Medicine › Internet, genomes & AI › mRNA vaccines
Karikó and Weissman's modified mRNA
2005 paper; Nobel Prize 2023· Person· Germs, drugs & genetics
Well documentedSolid records, physical evidence or scientific consensus.
Katalin Karikó and Drew Weissman found how to make messenger RNA usable as medicine without triggering harmful inflammation.
See it on the Technology & Medicine map →How it works
Hungarian-born biochemist Katalin Karikó spent years at the University of Pennsylvania trying to turn messenger RNA, the cell's working copy of a gene, into medicine, despite rejected grants and a 1995 demotion. With immunologist Drew Weissman, whom she met at a photocopier in 1997, she found why injected mRNA set off inflammation. Their 2005 paper showed that swapping one RNA building block, uridine, for a modified version let the mRNA slip past immune alarms.
Why it mattered
Their tweak is in both the Pfizer–BioNTech and Moderna COVID-19 vaccines, given billions of times, and opened mRNA to vaccines and therapies beyond.
Legacy and how we know
Their 2005 paper in the journal Immunity and follow-up work in 2008; University of Pennsylvania patents; the 2023 Nobel Prize in Physiology or Medicine, which cited the discovery directly.
Still unknown or debated
Many others built mRNA medicine, including Robert Malone's 1980s experiments and the 'lipid nanoparticle' fat wrappers from Pieter Cullis's circle; how to share credit is still argued.
Connections (2)
▸Genetic engineering (recombinant DNA) supplied the lab methods of Karikó and Weissman's modified mRNAMostly agreed
The connection
To make mRNA in the lab, Karikó and Weissman used tools born of genetic engineering: a target gene inserted into a circle of bacterial DNA (a plasmid), then copied into mRNA in a test tube by a viral enzyme. This method, in vitro transcription, came out of 1980s recombinant DNA work.
When and how
Douglas Melton and colleagues at Harvard described making RNA from plasmids in 1984; Karikó and Weissman used such methods at the University of Pennsylvania, 1990s–2005.
How sure are we?
Their 2005 paper's methods section describes in vitro transcription from DNA templates, a standard recombinant DNA technique.
Debates and open questions
In vitro transcription also leaves by-products, such as double-stranded RNA, that trigger inflammation; Karikó's team showed in 2011 that removing them also matters, and how much each fix contributes is still studied.
▸Karikó and Weissman's modified mRNA made possible mRNA vaccinesWell documented
The connection
Unmodified mRNA alarmed the immune system, causing inflammation and producing little protein. Karikó and Weissman's swap of uridine for a modified version solved that. Both the Pfizer–BioNTech and Moderna COVID-19 vaccines use a related building block, N1-methylpseudouridine, packed in lipid nanoparticles. Karikó had joined BioNTech in 2013, helping carry the method into its vaccine.
When and how
University of Pennsylvania, 2005 and 2008 papers; licensed onward to BioNTech in Mainz and Moderna in Massachusetts; vaccines authorized December 2020.
How we know
Vaccine ingredient lists show the modified building block; the 2023 Nobel citation credits the discovery with enabling effective mRNA vaccines against COVID-19.
Debates and open questions
CureVac's unmodified-mRNA COVID-19 vaccine managed only about 48% efficacy in 2021, supporting the modification's importance, though dose differences complicate the comparison.