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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#191
post #97

Earlier quoted context omitted.

A pairwise sequence alignment done with `needle` starts like this: BioNTech_Pfiz 1 -----------GAGAATAAACTAGTATTCTTCTGGTCCCCACAGACTCAG 39 |||||.|.|..|||| ||| || Moderna 1 GGGAAATAAGAGAGAAAAGAAGAGTA----------------AGA---AG 31 BioNTech_Pfiz 40 AGAGA----AC-------CCGCCACCATGTTCGTGTTCCTGGTGCTGCTG 78 |.|.| || |||||||||||||||||||||||||||||||| Moderna 32 AAATATAAGACCCCGGCGCCGCCACCATGTTCGTGTTCCTGGTGCTGCTG 81 BioNTech_Pfiz 79 C…

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…

Both sequences express the same protein.

Sequences are different because they are differently codon optimized. See https://en.wikipedia.org/wiki/Codon_usage_bias, especially "Effect on transcription or gene expression" section.

Re: Moderna mRNA sequence released to GitHub [pdf]

#192

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.

"Hepatitis C treatments" We don't really need the same quantities of that, though.

https://www.hhs.gov/hepatitis/learn-about-viral-hepatitis/da...

It can be said that hepatitis care is more necessary than covid.

Re: Moderna mRNA sequence released to GitHub [pdf]

#193

Earlier quoted context omitted.

"Hepatitis C treatments" We don't really need the same quantities of that, though.

https://www.hhs.gov/hepatitis/learn-about-viral-hepatitis/da... It can be said that hepatitis care is more necessary than covid.

The world is not in lockdown becuse of hepatitis, though.

Re: Moderna mRNA sequence released to GitHub [pdf]

#194
post #134

Earlier quoted context omitted.

Modern a has been working on mRNA since 2010 and mRNA vaccines since 2012. They have the process down pretty solid, but vaccines do not bring in the bacon.

" but vaccines do not bring in the bacon." As in, "do not generate enough income"? Really? Now?

Vaccines can be very lucrative. Pfizer has billions in sales for Pentacel.

Re: Moderna mRNA sequence released to GitHub [pdf]

#195

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…

It's an interesting structure, but probably partly out of patent law. To wit, SARS-nCoV-2 is non-patentable, being of natural occurance.

But a specific composition that encodes its spike protein, encapsulated in a lipid nanoparticle? That's much more of a creative work.

Re: Moderna mRNA sequence released to GitHub [pdf]

#196
post #16

so how are the first and the second dose different?

"Some vaccines require two doses because the immune response to the first dose is rather weak. The second dose helps to better reinforce this immune response." - I would have to think over time that could be optimized somehow to just require one w/ ML and test results, etc.

Re: Moderna mRNA sequence released to GitHub [pdf]

#197
post #70
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…

- 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 vectors)

- 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 And so many people have been killed by this overly conservative testing, phase ~<2.5 was enough

Re: Moderna mRNA sequence released to GitHub [pdf]

#198
post #195

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…

It's an interesting structure, but probably partly out of patent law. To wit, SARS-nCoV-2 is non-patentable, being of natural occurance. But a specific composition that encodes its spike protein, encapsulated in a lipid nanoparticle? That's much more of a creative work.

If it's just the spike protein encapsulated in a lipid nanoparticule (for isolation and transportation?), that looks like something not creative and quite established for people in the field of genetic material transport.

Re: Moderna mRNA sequence released to GitHub [pdf]

#199

Earlier quoted context omitted.

" but vaccines do not bring in the bacon." As in, "do not generate enough income"? Really? Now?

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 inaccessible to the poor and the third-world.

Re: Moderna mRNA sequence released to GitHub [pdf]

#200
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.

Any individual protein doesn't seem that complex since it's just a combination of some 20 amino acids, but the variations are endless: "Since each of the 20 amino acids is chemically distinct and each can, in principle, occur at any position in a protein chain, there are 20 × 20 × 20 × 20 = 160,000 different possible polypeptide chains four amino acids long, or 20n different possible polypeptide chains n amino acids…

proteins are also unique in that not just their sequence matters, but also their physical shape. 2 proteins can have the same sequence but a different physical shape, and therefore have different impacts on the body's chemistry. I started a PhD researching DSP methods for matching protein sequences and locations of amino acids. Fun stuff.
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