(E) We have now known for over a year the two companies that delivered the first two Covid-19 vaccines – BioNtech and Moderna, based on mRNA. What we are now all discovering are the two beautiful minds who pioneered mRNA-based therapeutics: Dr. Katalina Karikó and Dr. Drew Weissman.
Messenger RNA (mRNA) “is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.”
Two French doctors, François Jacob and Jacques Monod won the Nobel Prize in Medicine 1965 for mapping those intricate and self-regulating processes of mRNA that determine how genes are expressed or suppressed.
Professor Katalina Karikó started to explore the applications of mRNA in the early 80s, first at the University of Szeged in her native Hungary, and later at the University of Pennsylvania. She already believed at that time that mRNA could be used for antiviral therapies.
In 1990, Professor Jon Wolff, from the University of Wisconsin, and a team of researchers established the proof that proteins were detected following the ingestion of a mRNA molecule into a mouse:”Direct gene transfer into mouse muscle in vivo“.
But in the 90s, there was little interest from the research community in mRNA because the overall belief was that molecule was fragile and ephemeral, and would never work.
But when you have passion and persistence, you will change the world no matter what? No funding for your research or having lost your patents, none of those life toughest challenges will stop you! And, that is what the unstoppable Dr. Karikó did!
In 1998, and still at the University of Pennsylvania, Dr. Karikó joined Dr. Weissman initially to find a vaccine for the HIV based on mRNA, but later that collaboration builds the foundations of what synthetic mRNA is today.
One of the major contributions of Dr. Karikó was to discover how to modify the mRNA molecule so that it can be ingested into humans and be tolerated by the immune system.
She published in 2004 her findings with Dr. Weissman in “Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.“
And proposed later significant improvements:
- “Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability“
- “Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA development“
In 2010, Dr. Derrick Rossi, an assistant professor at Harvard University, co-founded Moderna with the specific goal of using mRNA molecules to reprogram adult cells so that they acted like embryonic stem cells (for more on Professor Rossi’s research read – “highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA“).
In 2013, Dr. Karikó joined BioNTech, and in 2014 published a paper with BioNTech’s co-founders, Dr. Ugur Sahin and Dr. Özlem Türeci, “mRNA-based therapeutics — developing a new class of drugs” which synthesizes the endless opportunities of mRNA as a drug:
- mRNA is a pivotal molecule of life, involved in almost all aspects of cell biology
- As the subject of basic and applied research for more than 5 decades, mRNA has only recently come into the focus as a potentially powerful drug class able to deliver genetic information
- Synthetic mRNA can be engineered to resemble mature and processed mRNA molecules as they occur naturally in the cytoplasm of eukaryotic cells and to transiently deliver proteins
- Recent advances addressed challenges inherent to this drug class and provided the basis for a broad spectrum of applications
- Besides cancer immunotherapies and infectious disease vaccines novel approaches such as in vivo delivery of mRNA to replace or supplement proteins, mRNA-based induction of pluripotent stem cells, or mRNA-assisted delivery of designer nucleases for genome engineering rapidly emerged and entered into pharmaceutical development
And, multiple clinical trials of mRNA therapeutics are today in the pipeline:
On November 8th 2020, the day of her daughter Susan Francia‘s birthday, two times Women’s rowing Olympic Gold medalist, successful Mom, successful daughter, Dr. Karikó is told about the upcoming announcement of the BioNTech Covid-19 vaccine.
On November 9th 2020, BioNTech and Pfizer announced the first vaccine for the SARS-CoV-2.
On December 23rd, 2020, Dr. Karikó and Dr. Weissman received their Covid-19 vaccines based on their foundational research on mRNA.
References
Dr. Katalina Karikó:
Dr. Drew Weissman:
Deeper dive into mRNA and the Covid-19 mRNA vaccine:
- This is the video of a very recent medical award for Dr. Karikó and Dr. Weissman from Brandis University – the award includes excellent presentations of their researches by themselves, and a great introduction from Dr. Derrick Rossi:
- Those two blog posts by Bert Hubert are a wonderful way to learn about mRNA when your background is in computer science:
Recent articles in the press:
- CNN:”She was demoted, doubted and rejected. Now, her work is the basis of the Covid-19 vaccine“
- BFM TV:”La femme qui peut sauver le monde“
Note: The picture above are Dr. Karikó (source: Wikipedia) and with Dr. Weissman (source: University of Pennsylvania).
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