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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#71
post #2

What are the purple and blue sections after the stop codon for? I read a little about the 3' region, but for the vaccine, are these sections taken from a particular natural human sequence, or specially engineered for something else?

That's the part that makes you randomly yell, "Hail Bill Gates!"

Re: Moderna mRNA sequence released to GitHub [pdf]

#72
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 long. For a typical protein length of about 300 amino acids, more than 10^390 (20^300) different polypeptide chains could theoretically be made. This is such an enormous number that to produce just one molecule of each kind would require many more atoms than exist in the universe."

Re: Moderna mRNA sequence released to GitHub [pdf]

#73

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…

a) Yes, you can translate a mature[1] mRNA sequence, codon by codon, from the start until the stop codon, and it will give you the sequence of the protein it encodes.

b) Coronaviruses have a RNA genome. Researchers extracted it from wild-type viruses and then sequenced it.

[1]: mRNAs can undergo several maturation steps, such as splicing, which removes regions that won’t be translated into protein.

Re: Moderna mRNA sequence released to GitHub [pdf]

#75

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…

Answers:

a) From the mRNA you can learn the amino acid sequence of the protein very quickly. You absolutely cannot (yet) learn the function of the protein from that sequence - normally, people just do comparisons with proteins whose functions ARE known. Oftentimes in enzymes there are "domains" or little functional regions that stay consistent over long periods of time, so that's a good way to assign function (given knowledge of other proteins in the same family)

b) Yep. Every virus at some point in their lifecycle use mRNA. You can just sequence the virus and get all that data (I've done that on SARS-COV-2, it's honestly pretty easy). Then you just do homology alignment (as stated above) and you can figure out approximately what each gene does.

The problem of de-novo protein prediction is ONE OF THE HARDEST PROBLEMS IN BIOTECH, but just like getting amino acid sequence, doing homology searches, sequencing viruses, etc, is basic biotech and I'd expect an eager high schooler or undergrad to be able to do them.

Re: Moderna mRNA sequence released to GitHub [pdf]

#76

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…

[deleted]

Re: Moderna mRNA sequence released to GitHub [pdf]

#78
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 think it's a bit like a private key- the difficulty is in finding some combination that works in an absolutely massive space of possible proteins, not necessarily in the length of the protein.

Re: Moderna mRNA sequence released to GitHub [pdf]

#79
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 is way more stable than RNA. Since you can easily synthesize RNA from DNA, and DNA synthesis technology is much more mature, folks normally synthesize DNA and then derive/make the RNA from it. That makes most researches default to DNA 5' to 3', even when talking about RNA.

Re: Moderna mRNA sequence released to GitHub [pdf]

#80

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…

No wonders some people have an allergic reaction. Those people's immune response is more sensitive to this change.
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