COVID-19 Diary – Day 274

The History of mRNA Vaccines, and the story of Katalin Karikó

With the recent approval of Pfizer/BioNTech’s COVID-19 vaccine and its usage to combat such a high profile virus as SARS-CoV-2, the term mRNA is suddenly being used much more frequently around the world. But not that long ago many in the pharmaceutical industry were quick to dismiss mRNA as a viable vaccine development method. In fact, it has taken over 40 years to get mRNA technology from the point of conception to the resounding success we now see! We would like to take a moment to share some of that history, and the building blocks of what lead to the world’s first approved COVID-19 vaccine.

The history of Pfizer’s COVID-19 vaccine, and in fact all future mRNA vaccines, can be traced back to a lab located at the Biological Research Centre (BRC) in Szeged, Hungary, where one young PhD student Katalin Karikó was working in 1978. Prof. Karikó used her time at the BRC to begin her research into messenger RNA (mRNA) and the ways it could be used to treat a variety of ailments, including cancer, damage from strokes, and of course viruses.

Katalin Karikó circa 1980

But Prof. Karikó’s time with the BRC came to an end in 1985, when her position was terminated. Shortly after, she moved to the US and took a teaching position at the University of Pennsylvania. Prof. Karikó continued to follow her passion, and in 1990 submitted a grant application to establish mRNA-based gene therapy. The grant was rejected, and she faced demotion over the failure to attract financial backing.

Despite repeated setbacks and lack of support from investors or fellow scientists, Prof. Karikó persisted and persevered. For years mRNA research had been stalled due to injections leading to inflammatory reactions in patients, but in 2004 Prof. Karikó and her colleague Drew Weissman discovered a solution. By slightly altering the nucleoside in the mRNA string, the serious side effect could be prevented! This discovery led to her published paper in 2005, on the impact of nucleoside modification and the evolutionary origin of RNA (read it here).

In 2008 in the city of Mainz (Germany) a husband and wife team of scientists, Dr. Ugur Sahin and Dr. Özlem Türeci, founded a hopeful pharmaceutical company by the name of BioNTech, with the goal of focusing on the development of technologies and drugs to improve individualized cancer immunotherapy efforts. One of the methods they began looking into was messenger RNA technology.

Dr. Ugur Sahin, left, and Dr. Özlem Türeci, right

Back in Pennsylvania, Prof. Karikó was continuing to hit roadblocks with the university, but in 2012 she and Drew Weissman were awarded a patent for their discovery of modified nucleosides for prevention of inflammation in mRNA injections. The University soon sold its IP license for the patent to Gary Dahl, the head of a company that eventually became Cellscript.

In early 2013 Prof. Karikó heard the news that two relatively new pharmaceutical companies, Moderna and AstraZeneca had reached a $240M deal to research a vascular endothelial growth factor treatment mRNA treatment. At this point, she knew that if she wanted to actually apply her knowledge and experience with mRNA technology, she would need to look beyond the University of Pennsylvania. Later that year she took the role of Senior Vice President at BioNTech RNA Pharmaceuticals.

Now working together with people who shared her passions, Prof. Kariko was finally able to lend her expertise with mRNA on various projects. Between 2014 and 2018 BioNTech filed for several patents for the use of their technology in the treatment of cancer and other serious diseases. Meanwhile, in 2018, the young pharmaceutical company Moderna made a licensing agreement with Cellscript to be able to use Prof. Karikó’s groundbreaking patent to reduce mRNA inflammation.

Work continued at both BioNTech and Moderna, looking at ways mRNA technology could be utilized to fight disease and repair damage. Both companies were aware that a treatment method like this could revolutionize the fight against disease forever, and the prospects for making it successful had only improved in the past years. Once all but ignored by the scientific community, mRNA technology was now being praised for being one of the safest and “cleanest” methods of vaccination, due to the quick protein-decay that leaves nothing but antibodies in the host system.

In late 2019, as we all know, a new virus, eventually designated as SARS-CoV-2 was discovered in China. On January 11th, 2020, Yong-Zhen Zhang, a scientist in China, made the genetic sequence of the virus available to the scientific community worldwide. Just 2 days later Moderna completed their design for a potential vaccine, known as mRNA-1273. Within a month that vaccine had been manufactured and Phase I trials were ready to begin.

Yong-Zhen Zhang

Over at BioNTech, in mid-January 2020 they instituted what they called “Project Lightspeed”. They quickly decided to consider 2 candidates for COVID-19 vaccines, and moved forward with animal testing and manufacturing right away. In mid-March 2020 they announced collaborative partnerships for funding and logistic support with Fosun and Pfizer and began their first human trials in April.

In the end, BioNTech would prove to be a little quicker to market with their final vaccine product, but Moderna’s vaccine could receive approval any day now as well.

So when you get your COVID-19 vaccination, and especially when we are able to once again live freely without risk of infection, please take a moment to thank Prof. Katalin Karikó, the mother of mRNA medicine, for her 42 years of work and perseverance. Or you could follow her on Twitter too!

Prof. Katalin Karikó – Mother of mRNA Medicine

That’s all for now, stay safe everyone!

Research Material:
https://en.wikipedia.org/wiki/Katalin_Kariko
https://www.telegraph.co.uk/global-health/science-and-disease/redemption-one-scientists-unwavering-belief-mrna-gave-world/
https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/
https://nypost.com/2020/12/05/this-scientists-decades-of-mrna-research-led-to-covid-vaccines/
https://biontech.de/covid-19
https://www.nytimes.com/2020/11/10/business/biontech-covid-vaccine.html
https://en.wikipedia.org/wiki/BioNTech
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-co-develop-potential-covid-19-vaccine
https://nymag.com/intelligencer/2020/12/moderna-covid-19-vaccine-design.html
https://www.sec.gov/Archives/edgar/data/1682852/000119312518323562/d577473ds1.htm
https://www.cellscript.com/

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