Analyzing The “Source Code” Of The COVID-19 Vaccine

Computer programs are written in code, which comes in many forms. At the lowest level, there’s machine code and assembly, while higher-level languages like C and Python aim to be more human-readable. However, the natural world has source code too, in the form of DNA and RNA strings that contain the code for the building blocks of life. [Bert] decided to take a look at the mRNA source code of Tozinameran, the COVID-19 vaccine developed by BioNTech and Pfizer.

The analysis is simple enough for the general reader, while nonetheless explaining some highly complex concepts at the cutting edge of biology. From codon substitutions for efficiency and the Ψ-base substitution to avoid the vaccine being destroyed by the immune system, to the complex initialisation string required at the start of the RNA sequence, [Bert] clearly explains the clever coding hacks that made the vaccine possible. Particularly interesting to note is the Prolase substitution, a technique developed in 2017. This allows the production of coronavirus spike proteins in isolation of the whole virus, in order to safely prime the immune system.

It’s a great primer and we can imagine it might inspire some to delve further into the rich world of genetics and biology. We’ve featured other cutting edge stories on COVID-19 too; [Dan Maloney] took a look at how CRISPR techniques are helping with the testing effort. If there’s one thing the 2020 pandemic has shown, it’s humanity’s ability to rapidly develop new technology in the face of a crisis.

50 thoughts on “Analyzing The “Source Code” Of The COVID-19 Vaccine

    1. What’s to moderate? At this point either the vaccine works, or it doesn’t. That’s the most important to people. The how, only to a much smaller group. We don’t even get to hack on it. What it does do for us however is show us techniques and knowledge that can be applied to a lot of other diseases that currently give us grief, like the common cold.

  1. The thing about viruses is that they like to incorporate other chunks of DNA into themselves.
    II suspect adding the machinery to generate 1-methyl-3’-pseudouridylyl into our bodies might well be a bad move in the long run.

    1. From the article:

      > “Many people have asked, could viruses also use the Ψ technique to beat our immune systems? In short, this is extremely unlikely. Life simply does not have the machinery to build 1-methyl-3’-pseudouridylyl nucleotides. Viruses rely on the machinery of life to reproduce themselves, and this facility is simply not there. The mRNA vaccines quickly degrade in the human body, and there is no possibility of the Ψ-modified RNA replicating with the Ψ still in there.”

      The vaccine does not contain information telling our body how to make 1-methyl-3’-pseudouridylyl, rather it contains RNA made *with* this molecule. As such, there is not a risk of either our body or viruses using this molecule if you get the vaccine.

    2. “The thing about viruses is that they like to incorporate other chunks of DNA into themselves.”

      You are confusing them with bacteria.

      “I suspect adding the machinery to generate 1-methyl-3’-pseudouridylyl into our bodies might well be a bad move in the long run.”

      A vaccine does not add machinery to our bodies.

    1. A better question might be to what extent this approach really is “tampering” with our systems.

      The DNA => RNA => protien => protienDoesStuff pathway is already the normal way our body works, do nothing problematic there. The only difference is bypassing the DNA => RNA part of that chain, and this actually makes it considerably safer. RNA doesn’t duplicate the way DNA does, and it breaks down quickly (unlike DNA). As such, this vaccine doesn’t really “tamper” with our system; it would be more accurate to say it uses our system as it’s meant to be used.

      1. Yep, we have complete understanding, and control over the building blocks of life. Maybe with the success of these GMO vaccines, consumers will be more accepting of GMO food products. Never really understood the fear. GMOs wouldn’t survive, if they weren’t safe and healthy…

        1. That is like saying we have complete control over Nuclear. The very worse case a serious, non military, Nuclear accident with the current safeguards might kill a hundred to a few thousand people before their time. Very worse case a deliberate Nuclear act might kill or sterilise a large percentage of the human population. MAD (Mutually Assured Destruction), has prevented mostly sane people from considering deliberate Nuclear acts of war for 70+ years. We have only detonated 2053 between 1945 and 1998 ( ref: https://www.youtube.com/watch?v=LLCF7vPanrY )

          With genetic manipulation, either an accident or deliberate act could in theory kill everything – there is only one type of DNA (ATCG – Adenine, Thymine, Cytosine and Guanine are the four nucleotides found in DNA, RNA contains Uracil instead of Thymine), ALL animals and plants share the same DNA, some overlap more than others. All it takes is one mistake and that could be all she wrote…

          Just because we have not made a bad mistake (yet), is truly brilliant. But the tools to manipulate DNA and RNA are in the hands of ANYONE who wants to manipulate them these days, which is something you can not say about the proliferation of concentrated nuclear materials. We only finished the Human Genome Project in 2003, which started in 1990. It took us 13 years to sequence the 3.2 billion base pairs. And 2012 was when Jennifer Doudna and Emmanuelle Charpentier published their Nobel winning paper on CRISPR-Cas9 genomic editing. So literally we have had less than 8 years, with insane powers of manipulation and no accidents (yet) or malicious acts. The hope would be that anyone with enough knowledge to do stupid things would be sane enough to not do so…

          Silly things like glow in the dark mice and pigs were created by splicing in bioluminescent jellyfish DNA, with no accidents (yet). But as times goes on the entry bar to manipulation drops lower and lower the fear, at least in my mind, is that the level of stupid things that are done will only increase. If I decided I could start manipulating DNA, just hope that if I do that I never say “oops”.

          1. Thanks for getting the sarcasm… We really don’t have complete understanding or control. We take snippets of code, and splice it into another ‘program’, and see if it works out as expected. We really don’t know exactly what we are splicing in, or all that might be included, with the parts we wanted. How many lifeforms have we built from the ground, up? This isn’t a strong field of interest for me, but it is interesting, and I read an occasional article, on breakthroughs. These new vaccines are of interest, as there is some likelihood of getting stuck with an arm load of the stuff, in the next year or so. The goal seems to be to vaccinate everybody on the planet, with something I’d consider still a little experimental. I won’t quit my job, to avoid getting stuck, but I’m not jumping ahead in line either.

          2. “With genetic manipulation, either an accident or deliberate act could in theory kill everything – there is only one type of DNA (ATCG – Adenine, Thymine, Cytosine and Guanine are the four nucleotides found in DNA, RNA contains Uracil instead of Thymine), ALL animals and plants share the same DNA, some overlap more than others. All it takes is one mistake and that could be all she wrote…”

            “Researchers Find More Than 1 Million Alternatives to DNA”
            https://www.extremetech.com/extreme/301888-researchers-find-more-than-1-million-alternatives-to-dna

          3. Relax, you’ll never get to manipulate DNA to an extend of perversion nature already does. Mutations, horizontal gene transfer, retrovirii, all that crap. No accident or mistake can ever be worse than what is happening every single second naturally.

      2. – I like the coding analogy… So we reverse engineered enough of a CPU/system that is closed source we can manage to execute some assembly code directly on it. – This seems to produce the output we’re after and not a BSOD – what could go wrong? (later) Huh, who would have guessed those instructions (or some of the fillers) would have overwritten the bootloader / changed the clock divider / etc?

        1. No. It does not contain any replication machinery, it only have a trivial mRNA for a synthesis of a single protein. No fancy protease to chop the resulting polypeptides into individual fragments, no RdRp to replicate the RNA, no means of rebuilding the capsid. Nothing even distantly resembling any viral machinery.

    2. no one knows for sure yet but probably this is the safest kind of genetic manipulation, because the synthetic mrna strand doesn’t encode instructions for replicating. a virus causes our cells to replicate itself but this vaccine causes our cells to replicate something else which itself cannot replicate further. so there might be unforeseen consequences but they probably won’t be synthetic-virus-pandemic sort of consequences. and for the most part, they will diminish as the mrna in the vaccine gets “used up.”

  2. From my understanding, in order to make the vaccine work properly, they needed to completely bypass the human immune response, as the immune system would normally detect and destroy the vaccine as if it was a real virus. Thus, the need to exploit a back door to the immune system that any man made virus can then exploit to deliver it’s engineered payload. To anyone educated in microbiology, is this layman’s understanding correct-ish?

  3. Ah.

    Whenever you deliver your next ASP snippet to your customer you also deliver the source code of however-the-current-Microsoft-dystopian-web-server-is-called-these-days, PLUS the OS’s source code, PLUS all the firmware stack (don’t forget harddisks, SSDs, network adapters, yadda, yadda) PLUS… you get the gist?

    Myself? I’m pretty excited that those things aren’t trade secrets this time around. This is *real progress* wrt the last time I looked.

  4. No. In this case, you /want/ DNA: first, it’s way more stable than mRNA; second, it’s pretty easy to replicate (typically you farm it out to some poor unsuspecting E. Coli by sneaking in a plasmid [1], i.e. the DNA packed as a double-helix “ring”, which the bacterium (more or less grudgingly) replicates).

    In a last step, that DNA is enzymatically copied to mRNA.

    It’s like making your lost-wax positives in a 3D printer and casting afterwards whenever you want a bronze gadget :)

    [1] https://en.wikipedia.org/wiki/Plasmid

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