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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#61

Post by schoen »

tablespoon wrote: post #52
puzzlingcaptcha wrote: post #48

Earlier quoted context omitted.

Here is a breakdown https://berthub.eu/articles/posts/reverse-engineering-source... discussed previously https://news.ycombinator.com/item?id=25538820

> This is somewhat of a problem for our vaccine - it needs to sneak past our immune system. 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. > So in the BioNTech/Pfizer vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. The really clever bit is that although this replacement Ψ pla…

In case others don't know this, the reason this is abbreviated Ψ (psi) is that Ψ is the first letter of Greek ψευδής 'false, lying', the origin of the prefix pseudo-.

Re: Moderna mRNA sequence released to GitHub [pdf]

#62

Post by fabian2k »

throwawaysea wrote: post #58
yrral wrote: post #6

Related: Here's a article from late last year describing and explaining the source code of Pfizer vaccine: https://berthub.eu/articles/posts/reverse-engineering-source... It's a very interesting read and I hope the author makes another post explaining the differences of the two mrna vaccines.

From that link: > The injection contains volatile genetic material that describes the famous SARS-CoV-2 ‘Spike’ protein. Through clever chemical means, the vaccine manages to get this genetic material into some of our cells. > These then dutifully start producing SARS-CoV-2 Spike proteins in large enough quantities that our immune system springs into action. Confronted with Spike proteins, and (importantly) tell-tale…

The mRNA is stable for a few hours or so, it is both chemically unstable in solution under the conditions in a cell and also actively degraded by various mechanisms.

Re: Moderna mRNA sequence released to GitHub [pdf]

#64

Post by [deleted] »

robbiep wrote: post #53
zappo2938 wrote: post #25

Wow Looks like it is analogous to having a header on a TCP packet. [0] Here is an animation of mRNA encoding translated to proteins inside a ribosome. [1] "The ribosome is composed of one large and one small sub unit that assemble around the messenger RNA, which then passes through the ribosome like a computer tape. The amino acid building blocks, that's the small glowing red molecules, are carried into the ribosome…

I ended up majoring in biochemistry and molecular biology in my undergrad because I was browsing on Wikipedia one day and came across an article written on an E. Coli variant that had sentences like: 01J3 e. Coli has a DNA Polymerase that contains 3k’-5’ proofreading capability and 5’-3’ error correcting with a polymerisation rate of 50bps I’ve made the above up because I have never been able to find a Wikipedia page…

[deleted]

Re: Moderna mRNA sequence released to GitHub [pdf]

#65

Post by carlmr »

seiferteric wrote: post #54
tablespoon wrote: post #52

Earlier quoted context omitted.

> This is somewhat of a problem for our vaccine - it needs to sneak past our immune system. 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. > So in the BioNTech/Pfizer vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. The really clever bit is that although this replacement Ψ pla…

Umm, isn't that kind of scary? Like could you create a virus with this Ψ that our immune system can't fight at all?

Maybe I'm thinking too simplified here, but wouldn't this only work on the first iteration? After all the virus would replicate with Us in your cells and then the replicas wouldn't have the advantage anymore.

Re: Moderna mRNA sequence released to GitHub [pdf]

#66

Post by rolph »

sp1rit wrote: post #51

If my little knowledge from biology class serves me correct, RNA uses Udenine instead of Thymine. But in this document it uses T. Can somebody explain to me why?

DNA uses base pairs [A,T] and [G,C], this code is for a piece of DNA,. if you keep a DNA sequence in vials for later use, that is much more stable and easier to manipulate, and repair when corrupted.

normally RNA in vivo is complexed with protiens that prevent RNA from folding, and annealing into structure that is not compatible with translation to protien. In the vaccine this isnt happening, this is why RNA is hard to work with and the vaccine must be kept so cold.

This is not to say that DNA is simple to work with, but it solves problems if you dont need direct access to RNA.

Re: Moderna mRNA sequence released to GitHub [pdf]

#67

Post by airhead969 »

andrewcl wrote: post #42

Cool, but it's the lipid delivery system that is the secret sauce. This is equivalent to giving the source code without a compiler to build it.

Wouldn't the "compiler" be the bioreactor used to mass-produce it and the "installer" be the lipid encapsulation? :)

Re: Moderna mRNA sequence released to GitHub [pdf]

#68

Post by IgorPartola »

seiferteric wrote: post #54
tablespoon wrote: post #52

Earlier quoted context omitted.

> This is somewhat of a problem for our vaccine - it needs to sneak past our immune system. 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. > So in the BioNTech/Pfizer vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. The really clever bit is that although this replacement Ψ pla…

Umm, isn't that kind of scary? Like could you create a virus with this Ψ that our immune system can't fight at all?

My exact question when I read that.

Re: Moderna mRNA sequence released to GitHub [pdf]

#69

Post by maxerickson »

seiferteric wrote: post #54
tablespoon wrote: post #52

Earlier quoted context omitted.

> This is somewhat of a problem for our vaccine - it needs to sneak past our immune system. 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. > So in the BioNTech/Pfizer vaccine, every U has been replaced by 1-methyl-3’-pseudouridylyl, denoted by Ψ. The really clever bit is that although this replacement Ψ pla…

Umm, isn't that kind of scary? Like could you create a virus with this Ψ that our immune system can't fight at all?

It's part of an instruction to cells to make something. Viruses replicate by instructing cells to make viruses. Our cells don't know how to make Ψ, so the replicated virus would have the normal instruction.

Re: Moderna mRNA sequence released to GitHub [pdf]

#70

Post by azernik »

drtz wrote: post #31

I'm sure it's more complex than I grasp as a layperson, but I'm utterly amazed at how simple this _appears_. I get the feeling that this is something I have a better chance of understanding than the average SaaS Terms and Conditions. I expected to have to scroll through pages upon pages of indecipherable text. Instead it's no bigger than a large paragraph of text, and I can easily fit it on my screen.

The protein they're trying to manufacture is indeed quite simple - AFAIU both BioNTech and Moderna put together their sequences in a weekend. (Though there was a more involved process of winnowing down the sequences for the most effective ones.)

The technically challenging parts are:

- delivery mechanism: you need to take a very unstable molecule, protect it from the environment - both external, and when inside the patient - and insert it into a human cell. (This is called the "platform", and is usually developed independently from the specific payload.)

- manufacturing: both producing the mRNA itself at a large scale, and inserting it into the delivery mechanism, at a large scale and in low-temperature conditions

- testing: the newly-developed payload and the existing platform were integrated at small scales within weeks, but testing the thing for safety and efficacy took months

EDIT: As schoen pointed out, this was not actually released by Moderna, but reverse engineered by third-party researchers. Original text was: "Hence they feel safe releasing this. Their moat is not the gene sequence, their moat is everything else."

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