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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#301

Post by phreeza »

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.

People tend to think of genetic code as a sort of assembly language which is very verbose, but I wonder if the correct way to view it is in fact a very terse domain-specific language, because it actually depends on the entire complex machinery of the cell to be present in order to work, which in itself contains a lot of information?

Re: Moderna mRNA sequence released to GitHub [pdf]

#302

Post by flobosg »

shellfishgene wrote: post #298
flobosg wrote: post #40

Earlier quoted context omitted.

Sequencing technologies have improved immensely over the last decade and a half. And, in this particular case, getting the sample RNA is incredibly easy, since its purity and integrity in the vial is quite high.

I didn't look at the details of how they sequenced it, but given that there are chemically modified bases in the mRNA vaccines there is a chance the normal methods for sequencing (and the first step of translating to DNA) don't work. Well, I guess in practice they did.

While not completely equal to the naturally occuring bases, the modified bases in the vaccine mRNA need to be able to complement to the non-modified ones present in tRNA anticodons during translation. If they can pair to their corresponding natural bases, then the chemically modified RNA can be also used as a template by the reverse transcriptase to generate the complementary DNA needed for the sequencing reaction.

Re: Moderna mRNA sequence released to GitHub [pdf]

#303

Post by TeMPOraL »

The_rationalist wrote: post #197
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…

- 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.) Sounds like a problem you solve once and for all, for any vaccine. And also that this problem was already solved since decades (e.g viral vector…

> Sounds like a problem you solve once and for all, for any vaccine.

I strongly doubt it. It's more like a problem you solve once for a particular class of payload and particular destination. Biology doesn't do packet switching - everything is just rapidly bumping into everything else at random, so your envelope needs to be designed in a way that's ignored by everything else than molecules at your target site, and it needs to not react with the payload it's carrying.

> And so many people have been killed by this overly conservative testing, phase ~

Overly conservative? That's what super-accelerated testing looks like. We're lucky it went well; had they screwed up, it would scare a lot more people away from vaccinating, lengthening the pandemic and increasing death toll.

Re: Moderna mRNA sequence released to GitHub [pdf]

#304

Post by alexobenauer »

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…

It is worth noting that the studies are still ongoing. The Phase 3 trials are two years.

Re: Moderna mRNA sequence released to GitHub [pdf]

#305

Post by DrAwdeOccarim »

o-__-o wrote: post #203
hcayless wrote: post #188

Earlier quoted context omitted.

The big money’s going to be in cancer treatments. If they can use this to target tumors, they’ll do quite well.

Bad news, it’s not looking very successful right now. Moderna is making back all the lost revenue with the emergency authorization tho

Can you share some of the bad news links? I've only seen the positive ones.

Re: Moderna mRNA sequence released to GitHub [pdf]

#306

Post by DrAwdeOccarim »

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.

But wasn't the whole Pfizer/BioNTech "secret sauce" leaked online after the EMA was hacked?

Re: Moderna mRNA sequence released to GitHub [pdf]

#307

Post by Tuna-Fish »

phreeza wrote: post #301
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.

People tend to think of genetic code as a sort of assembly language which is very verbose, but I wonder if the correct way to view it is in fact a very terse domain-specific language, because it actually depends on the entire complex machinery of the cell to be present in order to work, which in itself contains a lot of information?

Yes. Another important metaphor is that the common idea of DNA as blueprints is entirely wrong. It's not blueprints, it's a recipe. A blueprint describes what something is. A recipe describes the steps needed to make something, making use of a lot of complex existing machinery and parts with only a reference to them.

Re: Moderna mRNA sequence released to GitHub [pdf]

#308

Post by nraynaud »

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 way I see it we're just at the beginning, and we're mainly copy/pasting a lot of code, we understand some small parts, and generally in the teenage years of genome programming.

I don't know how long it will be before we get a bit more serious with it, but geneticists have a big obstacle in their understanding, any change might needs a thousand strong lifelong population study to be understood. That's way crappier than dumping the assembly or only having the documentation in Chinese.

I will add that moreover the developers might have been even more conservative in their code because they knew it was going for large scale deployment, they probably avoided the cutting edge as much as they could.

Re: Moderna mRNA sequence released to GitHub [pdf]

#309

Post by shellfishgene »

flobosg wrote: post #302
shellfishgene wrote: post #298

Earlier quoted context omitted.

I didn't look at the details of how they sequenced it, but given that there are chemically modified bases in the mRNA vaccines there is a chance the normal methods for sequencing (and the first step of translating to DNA) don't work. Well, I guess in practice they did.

While not completely equal to the naturally occuring bases, the modified bases in the vaccine mRNA need to be able to complement to the non-modified ones present in tRNA anticodons during translation. If they can pair to their corresponding natural bases, then the chemically modified RNA can be also used as a template by the reverse transcriptase to generate the complementary DNA needed for the sequencing reaction.

Generally I agree, but it could be the case that the modified bases work just well enough for tRNA matching in the ribosome, but not with the reverse transcriptase.

Re: Moderna mRNA sequence released to GitHub [pdf]

#310

Post by baq »

The_rationalist wrote: post #197
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…

- 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.) Sounds like a problem you solve once and for all, for any vaccine. And also that this problem was already solved since decades (e.g viral vector…

a bad vaccine could kill much more than that. remember that RNA vaccines are developed for 10+ years now and COVID19 is the first time they actually worked without side effects.
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