Good post, I read this when it was first published on that blog. Someone had posted it on HN. There is also a part 2 somewhere.

As someone who has a background in biology as well, I find it super reckless that we are doing this. There is absolutely no real evidence behind the safety of doing the following, specifically:

Ψ Substitution

Here we encounter our first surprise. The normal RNA characters are A, C, G and U. U is also known as ’T’ in DNA. But here we find a Ψ, what is going on?

We are now reaping the benefits of fundamental scientific research performed in the past. The discoverers of this Ψ technique had to fight to get their work funded and then accepted. We should all be very grateful, and I am sure the Nobel prizes will arrive in due course.

Many people have asked, could viruses also use the Ψ technique to beat our immune systems? In short, this is extremely unlikely. Life simply does not have the machinery to build 1-methyl-3’-pseudouridylyl nucleotides. Viruses rely on the machinery of life to reproduce themselves, and this facility is simply not there. The mRNA vaccines quickly degrade in the human body, and there is no possibility of the Ψ-modified RNA replicating with the Ψ still in there. “No, Really, mRNA Vaccines Are Not Going To Affect Your DNA“ is also a good read.

Usage of UTR from Alpha Globin Gene for Immediate Scheduling of Expression

In addition to this, the UTR also 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. This gene is known to robustly produce a lot of proteins. In previous years, scientists had already found ways to optimize this UTR even further (according to the WHO document), so this is not quite the alpha globin UTR. It is better.

Double Proline Substitution

In 2017 it was described how putting a double Proline substitution in just the right place would make the SARS-CoV-1 and MERS S proteins take up their ‘pre-fusion’ configuration, even without being part of the whole virus. This works because Proline is a very rigid amino acid. It acts as a kind of splint, stabilising the protein in the state we need to show to the immune system.