I am blown away by the tech used in BioNTech/Pfizer SARS-CoV-2 Vaccine.
#covid19 #vaccinology #vaccination
1/n
#covid19 #vaccinology #vaccination
1/n
First, they use mRNA to educate our immune system. This is the source code of it.
The CAP in first position acts like a file header. It has to be there otherwise nothing happens. (think like #! in Bash scripting).
2/n
The CAP in first position acts like a file header. It has to be there otherwise nothing happens. (think like #! in Bash scripting).
2/n
Second, our body runs a powerful antivirus system and will eliminate all foreign cells. It was found that if the U in RNA is replaced by a slightly modified molecule, our immune system loses interest.
3/n
3/n
So, the 5' UTR indicated "Untranslated region":
GAAΨAAACΨAGΨAΨΨCΨΨCΨGGΨCCCCACAGACΨCAGAGAGAACCCGCCACC
In the vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. This replacement Ψ calms our immune system, it is accepted as a normal U.
4/n
GAAΨAAACΨAGΨAΨΨCΨΨCΨGGΨCCCCACAGACΨCAGAGAGAACCCGCCACC
In the vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. This replacement Ψ calms our immune system, it is accepted as a normal U.
4/n
Third, the mRNA is "translated" into proteins using something called the Ribosome. It ingests a strand of RNA and based on that it emits a string of amino acids, which then fold into a protein.
6/n
6/n
The 5' UTR contains metadata: when should "translation" happen? And how much?
For the vaccine, they took the most ‘right now’ UTR they could find, taken from the alpha globin gene. (tandfonline.com/doi/full/10.10…)
7/n
For the vaccine, they took the most ‘right now’ UTR they could find, taken from the alpha globin gene. (tandfonline.com/doi/full/10.10…)
7/n
Then we have the “signal peptide” to tell where the produced proteins should go. There are differences between the viral and vaccine RNA: they use a clever technique to optimize the sequence...
8/n
8/n
RNA code can be listed in groups of 3 letters. This kind of groupe is called a codon. Multiple codons can encode the same amino acids. For example CUU and CUC make Leucine.
9/n
9/n
They optimized the viral RNA to include more Gs and Cs using codon synonyms. It turns out that RNA with a higher amount of Gs and Cs is converted more efficiently into proteins. All characters of the vaccine RNA are similarly ‘codon optimized’ to add a lot of C’s and G’s.
10/n
10/n
Lastly, they use a technique from 2017 called S-2P (ncbi.nlm.nih.gov/pmc/articles/P…) that makes the vaccine actually work. The goal of this technique is to substitute at the right place two codons of the virus by two Proline which stabilizes it.
11/n
11/n
At the end of the vaccine we find a ‘stop’ codon. The vaccine uses two UGA stop codons for safety perhaps?
12/n
12/n
Then the 3’ UTR: “The 3’-untranslated region plays a crucial role in gene expression by influencing the localization, stability, export, and translation efficiency of an mRNA .. despite our current understanding of 3’-UTRs, they are still relative mysteries”
13/n
13/n
According to the WHO document, the BioNTech/Pfizer vaccine 3’-UTR was picked from “the amino-terminal enhancer of split (AES) mRNA and the mitochondrial encoded 12S ribosomal RNA to confer RNA stability and high total protein expression”.
That is amazing.
14/n
That is amazing.
14/n
The final part of the mRNA is 'poly(A)'. It ends on a lot of "A". As the mRNA can be used many times, It can loose some of the A at the end. Once the A’s run out, the mRNA is no longer functional. In this way, the ‘poly-A’ tail is protection from degradation.
15/n
15/n
The whole vaccine creation process is super clever.
I hope you've enjoyed learning more about it. Thanks for reading 👋
16/n
I hope you've enjoyed learning more about it. Thanks for reading 👋
16/n
• • •
Missing some Tweet in this thread? You can try to
force a refresh
