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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#121

Post by outworlder »

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 reason I'm asking is to understand how the vaccine designers determine if there are any long-term effects of having this artificial material inside your body

The properties of mRNA are well known and have been for decades. Your cells are constantly producing more from the nucleus. It degrades, even more so when it gets transcribed. That's the beauty of this, it's self-limiting.

The only 'artificial' thing about it is the special base that's added to avoid detection by the immune system. Everything else is the exact same compounds present in your cells.

Re: Moderna mRNA sequence released to GitHub [pdf]

#122

Post by Ericson2314 »

batterseapower wrote: post #114
type_enthusiast wrote: post #110

Earlier quoted context omitted.

Knowing nothing about biotech – if Moderna and Pfizer were working from the same sequencing data, why would their resulting vaccine mRNA sequences be different? Even slightly? Edit: I guess what I'm asking is: presumably these vaccines both target the spike protein. Do both of these sequences express the same protein? Or is there a "close enough!" thing in the immune system, where it can be a little different and sti…

This very cool article explains the mRNA sequence chunk-by-chunk which might give you a flavour of why differences exist: https://berthub.eu/articles/posts/reverse-engineering-source...

> Our body runs a powerful antivirus system (“the original one”).

Awwww

Re: Moderna mRNA sequence released to GitHub [pdf]

#123

Post by atleta »

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…

Read the article, it answers your question in detail:

> The very end of mRNA is polyadenylated. This is a fancy way of saying it ends on a lot of AAAAAAAAAAAAAAAAAAA. Even mRNA has had enough of 2020 it appears.

> mRNA can be reused many times, but as this happens, it also loses some of the A’s at the end. Once the A’s run out, the mRNA is no longer functional and gets discarded. In this way, the ‘poly-A’ tail is protection from degradation.

Also, your cells continuously make mRNAs, depending on what proteins they need to synthesize. And those (have to) get discarded too. And also this is what happens to the actual viral RNA when the virus attacks you for real.

Re: Moderna mRNA sequence released to GitHub [pdf]

#124

Post by _joel »

wespiser_2018 wrote: post #100
azernik wrote: post #70

Earlier quoted context omitted.

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 p…

from what I've gathered, the rate limiting step for production as of yet, is creating the lipid vesicles and getting the RNA inside of them. Only a few companies have a process for this, and the supply chain for the precursors is limited as well.

Could be wrong but AFAIU the Pfizer one doesn't encapsulate in a lipid, hence why it needs lower temperatures.

Re: Moderna mRNA sequence released to GitHub [pdf]

#125

Post by dnautics »

azernik wrote: post #70
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 p…

sequence is actually released by Moderna in their patent:

https://www.modernatx.com/sites/default/files/US10702600.pdf

though they do present multiple sequences, so I guess you'd have to go to the FDA application to figure out exactly which one got used.

Re: Moderna mRNA sequence released to GitHub [pdf]

#126

Post by dylan604 »

azernik wrote: post #70
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 p…

> put together their sequences in a weekend

meh, I could do that over a weekend never sounded so scary, or impressive at the same time. That weekend just so happened to stand on the shoulders of prior decades of research though.

i guess this is big pharma's version of `apt-get install`

Re: Moderna mRNA sequence released to GitHub [pdf]

#127

Post by babypuncher »

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?

1) As someone else pointed out, this molecule substitution would not persist during replication. New viruses being produced in your cells would be made with a normal "U".

2) Your immune system does not usually attack the RNA housed inside a virus, but rather protein fixtures on its "body".

Re: Moderna mRNA sequence released to GitHub [pdf]

#128

Post by softwaredoug »

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.

Great quote from Maurice Hilleman, creator of many (most?) of our childhood vaccines goes something like “Don’t be smart. Instead be careful and accurate”

Lots of these things aren’t complicated. It’s the careful systematic testing and public trust building that’s the hard part.

Re: Moderna mRNA sequence released to GitHub [pdf]

#129

Post by throwawaysea »

atleta wrote: post #123
throwawaysea wrote: post #58

Earlier quoted context omitted.

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…

Read the article, it answers your question in detail: > The very end of mRNA is polyadenylated. This is a fancy way of saying it ends on a lot of AAAAAAAAAAAAAAAAAAA. Even mRNA has had enough of 2020 it appears. > mRNA can be reused many times, but as this happens, it also loses some of the A’s at the end. Once the A’s run out, the mRNA is no longer functional and gets discarded. In this way, the ‘poly-A’ tail is pro…

Can you explain what "discarded" means there? Does the body somehow flush it out?

Re: Moderna mRNA sequence released to GitHub [pdf]

#130

Post by grey413 »

ur-whale wrote: post #57

What this does, as a non-biotech person, I believe I understand at a high level: plonk this code into a ribosome and out comes the desired protein. What I don't understand is: a) how the m-RNA code relates to the produced protein (i.e I can read C-code and get an idea of what is does fairly quickly, but can the same be said of m-RNA and the resulting protein)? b) how did they get their hands on that code in the first…

Everyone else has had good answers, but I'm also going to note that we knew a ton about covid's general molecular biology well before it ever came into existence. Covid (more properly, SARS-CoV-2) is a cronovirus. Cronoviruses have been studied for some time since some of them cause common colds, and studied very intensely since 2002 when SARS showed pandemic potential. So when Covid showed up, there was a ton of prestablished information and expertise avaliable to help every element of the pandemic response.
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