2023’s Nobel Prize: Modifying mRNA to Resist Immune Response

The Nobel Prize is the most prestigious award in science. Katalin Karikó, PhD and Drew Weissman, PhD had the great honour of receiving this year’s prize in Medicine or Physiology for their work on mRNA. 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.

Behind the scenes of PKR

PKR is a protein that inhibits the 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 the translation of mRNAs into foreign and 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, so 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), meaning that if there is a mixture of both types of foreign mRNAs, the 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 pioneered a new way of treating pathologies. We now manage to get our bodies to produce the proteins that we want quickly and without the scare of genetic alterations. 

If you found this article interesting and want to take part in shaping the future, stay tuned and stay curious with us! You can read the entire article here. See ya’ later!

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.

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