Moderna mRNA sequence released to GitHub [pdf] • Hacker News Board

Re: Moderna mRNA sequence released to GitHub [pdf]

#231

Post by jcims » Tue, Mar 30, 2021, 3:43 AM UTC

mikehollinger wrote: post #167

dnautics wrote: post #125

Earlier quoted context omitted.

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.

Reading the primary claim is fascinating: "A composition, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle." I have a "I'm sure that means something to somebody" feeling. It's also surprising that the remaining claims seem to describe the resulting bits of the sequence, and that that…

This is a great animation of the life cycle of an HIV virus. It’s not exactly what happens with the pandemic virus but it gives you a good idea of the complexity of the process of viral reproduction (vaccine or immune response isn’t covered here):

https://vimeo.com/260291607

Animation of transcription from mRNA: https://youtu.be/TfYf_rPWUdY

Re: Moderna mRNA sequence released to GitHub [pdf]

#232

Post by takeda » Tue, Mar 30, 2021, 3:45 AM UTC

obilgic wrote: post #16

so how are the first and the second dose different?

I believe only Sputnik vaccine has different first and second dose, but their vaccine is of different category (it belongs to the same as AstraZeneca and Johnson and Johnson). The reason is that these vaccine use a vector (adenovirus) and there's a risk that body will develop antibodies for the vector and the second dose might not be as effective.

Re: Moderna mRNA sequence released to GitHub [pdf]

#233

Post by andagainagain » Tue, Mar 30, 2021, 3:46 AM UTC

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.

I'm estimating roughly 90-ish characters in a row, roughly 40 rows encoding the spike protein. So about 3600 base pairs. There are 3 base pairs per amino acid, so That's 1200 amino acids.

For comparison, the smallest chain that they technically call a protein is 100 amino acids that's an arbitrary limit to separate proteins from enzymes. So this thing isn't tiny tiny.

But Titin (also called connectin), a giant protein responsible for passive elasticity in mucles, is ~27,000-35,000 amino acids. So this thing isn't even close to the biggest proteins out there.

Re: Moderna mRNA sequence released to GitHub [pdf]

#234

Post by lowdanie » Tue, Mar 30, 2021, 4:00 AM UTC

mrfusion wrote: post #230

lowdanie wrote: post #228

Earlier quoted context omitted.

There is a system that transports protein fragments to the cell surface and “presents” them to the immune cells: https://en.m.wikipedia.org/wiki/Antigen_presentation

Thanks. So what makes that happen in this case? Is it because internally the cell doesn’t recognize the protein? Or it does this for all proteins it makes? Does say some hemoglobin get transported to the cell surface?

Yes, the even healthy cells are constantly transporting protein fragments to the cell surface but the immune system learns to ignore these as it is developing.

In addition, B and T cells only detect fragments on the surface of active Dendric cells. Dendric cells become active in response to alternate and less specific indications of infection such as an unusually high amount of mRNA translation or families of protein that occur only in bacteria and viruses.

Re: Moderna mRNA sequence released to GitHub [pdf]

#235

Post by squarefoot » Tue, Mar 30, 2021, 4:01 AM UTC

As a software/hardware guy who knows less than zero about the subject: is this something that (given the right resources) makes possible to replicate the vaccines? I mean in countries where they can't afford enough vaccines but already have or could invest in the ability to replicate them without caring about patents.

Re: Moderna mRNA sequence released to GitHub [pdf]

#236

Post by nielsbot » Tue, Mar 30, 2021, 4:01 AM UTC

jcims wrote: post #231

mikehollinger wrote: post #167

Earlier quoted context omitted.

Reading the primary claim is fascinating: "A composition, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle." I have a "I'm sure that means something to somebody" feeling. It's also surprising that the remaining claims seem to describe the resulting bits of the sequence, and that that…

This is a great animation of the life cycle of an HIV virus. It’s not exactly what happens with the pandemic virus but it gives you a good idea of the complexity of the process of viral reproduction (vaccine or immune response isn’t covered here): https://vimeo.com/260291607 Animation of transcription from mRNA: https://youtu.be/TfYf_rPWUdY

It blows my mind to see how life (and death) work at the molecular level--it's almost like some kind of manmade machine, but far more subtle and complex.

Re: Moderna mRNA sequence released to GitHub [pdf]

#237

Post by lettergram » Tue, Mar 30, 2021, 4:03 AM UTC

wombatpm wrote: post #218

lettergram wrote: post #45

Earlier quoted context omitted.

It really is that “simple.” Getting it designed and building it is more difficult. At its core, it’s a piece of mRNA that creates a protein. That code gets transcribed into a protein (often those are relatively short). That protein then triggers your bodies immune response, which trains it to attack covid19. Inject this mRNA into a cell and it’ll create the protein. Anything can be injected at this point once the mec…

Which makes me wonder. Could you place the entire virus genome in these liposomes and get them to hijack the machinery to make an entire virus? Like plasmid but for viral structures?

Yes, that's one of the concerns many have about this technology. Literally, anything can be injected and done at this point.

Not sure where the technology is exactly at, but I suspect we're no more than 5 years from major incident related to this.

Even this vaccine, we really don't know the long-term impacts or risks involved with this. For instance, this vaccine does appear more risky than the standard flu vaccine:

https://wonder.cdc.gov/controller/saved/D8/D137F981

Presumably this is due to increased inflammation. It's not hard to imagine that we'll be doing genetic editing soon enough with this (if we aren't already).

Re: Moderna mRNA sequence released to GitHub [pdf]

#238

Post by JonathonW » Tue, Mar 30, 2021, 4:04 AM UTC

jcims wrote: post #231

mikehollinger wrote: post #167

Earlier quoted context omitted.

Reading the primary claim is fascinating: "A composition, comprising: a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a betacoronavirus (BetaCoV) S protein or S protein subunit formulated in a lipid nanoparticle." I have a "I'm sure that means something to somebody" feeling. It's also surprising that the remaining claims seem to describe the resulting bits of the sequence, and that that…

This is a great animation of the life cycle of an HIV virus. It’s not exactly what happens with the pandemic virus but it gives you a good idea of the complexity of the process of viral reproduction (vaccine or immune response isn’t covered here): https://vimeo.com/260291607 Animation of transcription from mRNA: https://youtu.be/TfYf_rPWUdY

Coronavirus replication is pretty dramatically different from HIV replication-- coronaviruses are not retroviruses, and do not have a step where viral RNA is converted into DNA and integrated into the host cell's genome. Instead, coronavirus RNA is directly interpreted by the cell's ribosomes to make the proteins that ultimately build and comprise the replicated viruses.

The mRNA vaccines work in much the same way-- it's just that the mRNA vaccines only include the code for the spike protein and not the rest of the virus's machinery. So you get the vaccine and your body produces a bunch of spike protein by itself, which gives your immune system the opportunity to learn how to identify and react to the spike protein before it sees it on a real virus.

Re: Moderna mRNA sequence released to GitHub [pdf]

#239

Post by flobosg » Tue, Mar 30, 2021, 4:15 AM UTC

andagainagain wrote: post #233

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.

I'm estimating roughly 90-ish characters in a row, roughly 40 rows encoding the spike protein. So about 3600 base pairs. There are 3 base pairs per amino acid, so That's 1200 amino acids. For comparison, the smallest chain that they technically call a protein is 100 amino acids that's an arbitrary limit to separate proteins from enzymes. So this thing isn't tiny tiny. But Titin (also called connectin), a giant protei…

> that's an arbitrary limit to separate proteins from enzymes

Do you mean “to separate polypeptides from proteins”? Enzymatic activity has nothing to do with size. For example, one of the smallest enzymes in humans has 62 amino acid residues. And, under certain conditions, even single amino acids can be catalytic.

But yeah, the polypeptide-protein threshold can get fuzzy, especially with the recent advances in miniprotein characterization.

Re: Moderna mRNA sequence released to GitHub [pdf]

#240

Post by adgjlsfhk1 » Tue, Mar 30, 2021, 4:20 AM UTC

failwhaleshark wrote: post #199

hadlock wrote: post #154

Earlier quoted context omitted.

Current pricing for mRNA vaccines is something in the $4-7 dollars (that's $7.00 dollars, not $7,000.00 dollars) range. Compare that to one of the Hepatitis C treatments, which costs north of $350,000 by several accounts. Even remdesivir is something like $3000 for a course.

There are roughly 75 million HCV infections in the world. That translates to a total cure cost of: 75M * $350k = $26.25T There are other ARV treatments available which cost now roughly $50-100k and cure in 3 months. Whereas immunizing everyone against coronaviruses currently costs: 8B * $7 = $56B Clearly, the costs of the HCV cure are predatory and unreasonable because it doesn't lead to eradication and it's inaccess…

It's also worth noting that if it's $7 for the payer, there's a lot less than $7 of profit.