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How mRNA therapeutics went from being an overlooked & underfunded idea to the strongest weapon in our arsenal to fight the virus. Dr. Karalin Karikó is one of the scientists behind this revolution and her life is a story of sheer grit and optimism in the face of failure — Thread.
2/ Just a decade after the discovery of mRNA in 1961, scientists were considering injecting customized mRNA to turn cells into protein making factories. Dr. Karikó first heard about these ideas in the 70s as a young undergraduate at the University of Szeged in Hungary.
A "primer"
for non-biologists:
mRNA is a molecule which interprets genetic instructions stored in DNA and converts them into proteins. The idea is to hack this machinery by injecting mRNA which can make proteins our interest - in case of COVID vac, the viral spike protein.
for non-biologists: mRNA is a molecule which interprets genetic instructions stored in DNA and converts them into proteins. The idea is to hack this machinery by injecting mRNA which can make proteins our interest - in case of COVID vac, the viral spike protein.
3/ Back to our story. Being inspired by RNA biology, Dr. Karikó went on to join the lab of Prof. Jenö Tomasz in Szegad for her PhD and eventually moved to the US in 1985, with her husband and a 2-year old daughter to join Temple University as a postdoc.
4/ In 1990, when she started writing grant applications to establish mRNA-based gene therapies, she was offered a tenure-track position at the University of Pennsylvania. She was set to become a full Professor in a few years! The research was promising.
5/ By then people had figured out a way to make artificial RNA but there was another problem — mice injected with RNA showed a severe inflammatory immune response making human trials impossible. There was no way to move forward without getting over this hurdle.
6/ Hope was scarce & by mid-90s, Dr Karikó was struggling to get funds. In a big setback, she was demoted from her tenure-track position at UPenn. If that wasn't enough, in the same week she was diagnosed with cancer while her husband was stranded abroad due to VISA issues!
7/ But she was determined to pursue the problem. She accepted the demotion & continued working at the university for reduced wages. Luckily for her (and the world), her decision to stay led her to an exciting meeting which renewed her optimism for her work!
8/ In 1997, she met acclaimed immunologist Drew Weissman. “I met him at the Xerox machine and told him I could make any RNA,” Karikó recalled. In 2005, the duo figured out a way to avoid an immune response by making specific modifications to the mRNA. https://pubmed.ncbi.nlm.nih.gov/16111635/
9/ This was a big breakthrough! The following year, they tried to build a company to commercialise their discovery, but they failed to reach clinical trials while the university sold the rights to their patent to a third-party.
10/ While Karikó and Weissman struggled to build a company, in 2010, Dr. Derrick Rossi, then a postdoc at Stanford and intrigued by the duo's 2005 paper, co-founded Moderna to bring mRNA therapeutics and vaccines to the market.
11/ In 2013, Dr. Karikó asked UPenn to promote her back to the position she was demoted from in 1995 or she would leave and join the German company, BioNTech. ”When I told them I was leaving, they laughed at me and said, ‘BioNTech doesn’t even have a website.’"
12/ 7 years later, BioNTech has a website, a market cap of $25bn and along with Pfizer and Moderna, it is a leading company in developing effective COVID-19 vaccines. Dr. Karikó is now a Senior VP at BioNTech.
13/ We owe Dr. Karikó, Dr. Weismann and everyone else involved, a great debt of gratitude. I am sure there are hundreds of scientists like her who don't lost hope despite setbacks and a demoralizing system.
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#AcademicChatter #AcademicTwitter @KaushikLab
