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Comment by zevv | Hacker News Reader

My knowledge of modern genetic engineering is limited to some popsci literature, so I understand only parts of this story. I was surprside by this part though:

"Over many years of experimentation, it was found that if the U in RNA is replaced by a slightly modified molecule, our immune system loses interest. For real. [...] The really clever bit is that although this replacement Ψ placates (calms) our immune system, it is accepted as a normal U by relevant parts of the cell."

This sounds like a serious backdoor or attack vector to me - would there be any risk in introducing this Ψ, allowing some natural occuring permutations to turn wild or dangerous?

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I'm not an expert in this issue. But the Wikipedia article has the following statement:

"There are 11 pseudouridines in the Escherichia coli rRNA, 30 in yeast cytoplasmic rRNA and a single modification in mitochondrial 21S rRNA and about 100 pseudouridines in human rRNA indicating that the extent of pseudouridylation increases with the complexity of an organism."

So at first it shows, that Pseudouridine is not something completely new in nature. It exist for a long time already. And it seems a higher amount signals to the immune system, that this RNA is more human like and not coming from a virus. Since this mechanism seems to be established in nature I think one can assume it is safe. If it wouldn't be safe, viruses would probably already exist, which would make use of this "backdoor".

https://en.wikipedia.org/wiki/Pseudouridine

Thank you! I came here to ask the same question.

Now that we are producing and injecting industrial quantities of Ψ, any chance this will get incorporated in actual viruses or maybe teach the immune system not to ignore it (or maybe even go crazy about it)?

They're injecting already-made Ψ, not any of the genetic instructions that would enable cells/viruses to make their own Ψ.

But the broader concern about advances in biotech being potentially very dangerous is I think a very good one..

I think there's no risk since cells can't make Ψ, and probaby Ψ is not super durable as a chemical.

> cells can't make Ψ

Pseudouridine is the most common RNA modification in cells, actually. They produce it all the time.

> and probaby Ψ is not super durable as a chemical.

Quite the opposite. Pseudouridine usually increases the stability of the RNA molecule it modifies.

Taken from the article (probably after an update):

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.

I should have cleared that up. Normally Ψ would stand for pseudouridine, but the vaccine has a further modified base, 1-methylpseudouridine.

Cells might not, but people can...

The article directly addresses that question, saying it's highly unlikely because the viruses don't have the machinery to manufacture it.

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