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Moderna mRNA sequence released to GitHub [pdf]

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Re: Moderna mRNA sequence released to GitHub [pdf]

#331
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.

> To wit, SARS-nCoV-2 is non-patentable, being of natural occurance.

Looks man-made (modified in a lab) by most informed people.

Re: Moderna mRNA sequence released to GitHub [pdf]

#332
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…

> 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`

Not only did Moderna have a decade of experience with mRNA as 'drug', but the mechanism of coronavirus infection was well-understood from SARS research, namely the importance of the spike protein. All the parts were in place and just waiting for the specific SARS-CoV-2 sequence. They designed it as soon as they had access to the Wuhan sequence.

Re: Moderna mRNA sequence released to GitHub [pdf]

#333
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…

Would it be possible to use the same delivery mechanism for other mRNA sequences?

Almost certainly - e.g. the J&J vaccine (a DNA vaccine, not mRNA, but same principle) is using a viral delivery platform that they'd had sitting on the shelf for years and have used for other vaccines.

After the massive capex that has gone into mass-production of encapsulated mRNA delivery systems, I suspect this new technology will be very cost-competitive for the big markets like the annual flu vaccine.

Re: Moderna mRNA sequence released to GitHub [pdf]

#334
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.) The most amazing thing is that now that the platform is proven secure in dozens of millions of people, it should be be very easy and fast to g…

Even if the platform is safe, the payload itself needs to have its safety proven. Remember, the payload is just instructions, and those instructions make your cells pump out oodles of arbitrary proteins. That in itself can cause health problems. see e.g. the AstraZeneca vaccine's safety issues, which were caused IIUC by immune responses to the manufactured proteins. DNA vaccine, not mRNA, but the principle is the same.

re: cancers, that is actually what this technology was originally developed for! Moderna has been spending about a decade getting this tested and proven out for the cancer role, and they're quite close. From my quick reading of the literature, there seems to be some regulatory confusion about how exactly to run approval for this kind of personalized drug design (testing the method of generating the individual drugs?), but the bar is usually much lower for cancers with high mortality rates.

Re: Moderna mRNA sequence released to GitHub [pdf]

#335
post #231

Earlier quoted context omitted.

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

The "SARS-CoV-2 entry" video was really interesting too, and I recommend watching them both to see how they are different. https://vimeo.com/510310488

Nice!!! I didn’t even notice that was uploaded! The differences between HIV and SARS-CoV-2 makes me wonder what reliability there is in this process, and if some viruses are more reliably able to enter the cell than others (presumably those that are more infectious?)

Re: Moderna mRNA sequence released to GitHub [pdf]

#337

Earlier quoted context omitted.

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.

Interesting reasoning. But isn't it true to say that the "complex existing machinery and parts" which interprets the DNA was itself put together from instructions found in other DNA? I suppose that metaphors are rarely entirely comparable.

Re: Moderna mRNA sequence released to GitHub [pdf]

#338
post #263

The Human Genome Project was completed almost two decades ago, and somebody solved the protein folding problem recently. Why are we still doing genetics at the machine code level? Shouldn't we have some compilers, assemblers and linkers by now?

Because the problem is significantly more complicated than sequencing and folding.

Re: Moderna mRNA sequence released to GitHub [pdf]

#339
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…

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.

Usually you can't patent facts. If it is natural (not synthetic) gene sequence they shouldn't be able to patent it...
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