The Nobel Prize is the most prestigious award in science. Katalin Karikó, PhD and Drew Weissman, PhD had the great honor of receiving 2023’s prize in Medicine and Physiology for their work on modifying mRNA in order to resist the immune response. It led to the production of the COVID-19 vaccine, undoubtedly one of the most influential inventions of the last few years.
But what did the winners actually discover? Well, let’s dive into the wonderful molecular world of our bodies. We have a protein called PKR (RNA-dependent protein kinase), a soldier of our immune response. The researchers found that it does not efficiently bind RNA with modified bases. Here is how it works.
Into the world of proteins
PKR is a protein that inhibits translation of mRNA. PKR is activated by many kinds of foreign RNAs, be it double or single stranded, long or short (like those that could be found in RNA viruses). On the one hand, this protein is useful for our immune response. It is able to stop translation of mRNAs into foreign, maybe harmful proteins. On the other hand, it prevents the human body from receiving lab-made helpful mRNA.
The laureates found that pseudouridine (Ψ) enriched mRNA is translated more efficiently than unmodified mRNA. They theorized that it may have something to do with PKR, so they started testing. At first, they transcribed some mRNAs in vitro, using modified nucleotides. Then they compared modified with unmodified mRNA. mRNA enriched with Ψ activated PKR less. Therefore its translation is less inhibited. However, when PKR was inactive/absent in the cell, there was no difference in the rate of translation of modified and unmodified mRNA. Moreover, they confirmed that modified mRNA is not a competitive inhibitor (it doesn’t bind well to PKR). This means that if there is a mixture of both types of foreign mRNAs, translation would still be inhibited.
Even though there are some differences between in vitro and in vivo, it is needless to say that this paper had pioneered a new way of treating pathologies. We now managed to get our bodies to produce proteins that we want quickly and without the scare of genetic alterations.
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About the author…
Hi, my name’s Teodor, a second year medical student. I am a science enthusiast, amateur speedcuber, hardcore metalhead, and dedicated weeb.