[HN Gopher] Moderna mRNA sequence released to GitHub [pdf]
___________________________________________________________________
Moderna mRNA sequence released to GitHub [pdf]
Author : aty268
Score : 211 points
Date : 2021-03-29 21:11 UTC (1 hours ago)
(HTM) web link (github.com)
(TXT) w3m dump (github.com)
| koeng wrote:
| The thinking behind attaching a PDF with colors and not a Genbank
| file is why we can't have nice things in biotechnology.
| rubatuga wrote:
| Wait, you mean you don't extract genomic data from Excel? The
| MARCH1 gene brings many interesting surprises.
| chromatin wrote:
| I am fond of September 2, myself.
|
| For those not in the know:
|
| https://genomebiology.biomedcentral.com/articles/10.1186/s13.
| ..
| flobosg wrote:
| My thoughts exactly!
| julienchastang wrote:
| Exactly. FAIR (Findable, Accessible, Interoperable and
| Reusable) principles are at a loss here [1]. The "Reusable"
| part seems to be especially problematic as the sequence is
| buried in a PDF file though all aspects of FAIR are compromised
| here.
|
| [1] https://www.nature.com/articles/sdata201618
| brian_herman wrote:
| Here you go! https://github.com/brianherman/Assemblies-of-
| putative-SARS-C...
| [deleted]
| nsxwolf wrote:
| ELI5, Why are the sequences different if they result in the same
| spike protein?
| shakow wrote:
| I didn't check it was the only explanation, but the DNA ->
| protein encoding is surjective.
| controlweather wrote:
| 7 years from now everyone is infertile. Wonder why
| andrewcl wrote:
| Cool, but it's the lipid delivery system that is the secret
| sauce. This is equivalent to giving the source code without a
| compiler to build it.
| airhead969 wrote:
| Wouldn't the "compiler" be the bioreactor used to mass-produce
| it and the "installer" be the lipid encapsulation? :)
| snuxoll wrote:
| InstallGene by Flexera
| aty268 wrote:
| 'A group of Stanford researchers has hacked Moderna's messenger
| RNA (mRNA) vaccine for the novel coronavirus, Motherboard first
| reported on Monday, and published its entire genetic sequence on
| the open-source code repository Github.'
|
| https://gizmodo.com/stanford-scientists-post-entire-mrna-seq...
| throwawaysea wrote:
| What does "hacked" mean here? The article makes it sound like
| this wasn't something illegal:
|
| > Fire and Shoura told Motherboard that they had received
| permission from the FDA to collect scraps of vaccines that
| wouldn't have otherwise been used from empty vials and that
| they'd notified Moderna in advance of their plans to publish
| the sequence without receiving any objection in turn.
|
| Also:
|
| > The research team told Motherboard that they didn't "reverse
| engineer" the vaccine, they simply "posted the putative
| sequence of two synthetic RNA molecules that have become
| sufficiently prevalent in the general environment of medicine
| and human biology in 2021."
|
| I'm not familiar enough with how these sequences to work to
| understand what's being discussed. Is it simply that they took
| a sample of the vaccine and studied its composition using some
| standard machine/process?
| flobosg wrote:
| > Is it simply that they took a sample of the vaccine and
| studied its composition using some standard machine/process?
|
| That's exactly what they did.
| p0rkbelly wrote:
| obligatory:
|
| "I could have done this in a weekend"
| obilgic wrote:
| so how are the first and the second dose different?
| hfjfktmtkrn wrote:
| The second dose is like seeing someone stalking you for the
| second time.
|
| You should really do something about it because it's probably
| serious.
|
| The same way, the immune system gets really triggered when it
| sees the same thing which it supposedly cleared at a later
| date.
| meepmorp wrote:
| They're the same. It's just a second dose as a booster.
| joeyh wrote:
| My first thought was `wdiff pdizer moderna`. It's short enough to
| post here in its entirity, but I guess I had better not, anyway
| it's easy enough to extract from the pdf. Add a space after every
| letter and wdiff can find the common sequences nicely.
|
| Short except for flavor, this is from near the beginning:
|
| A[-G-]AGA{+A+}GAA{+ATATAAGAC+}CCCG{+GCGCCG+}CCACCATGTTCGTGTTCCTGG
| TGCTGCTGCC[-T-]{+C+}
| koeng wrote:
| Us folks in biotech have a special tool just for this :)
| https://blast.ncbi.nlm.nih.gov/Blast.cgi
|
| Unfortunately, the core algorithm dates back to 1990, so it can
| be real slow in some cases. Biotech takes a while to improve :(
| flobosg wrote:
| I think you meant
| https://www.ebi.ac.uk/Tools/psa/emboss_needle/ or
| https://www.ebi.ac.uk/Tools/psa/emboss_water/ ;-)
| flobosg wrote:
| 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
| CCTCTGGTGTCCAGCCAGTGTGTGAACCTGACCACCAGAACACAGCTGCC 128
| ||.||||||..|||||||||.|||||||||||||||.|.||.||||||||
| Moderna 82
| CCCCTGGTGAGCAGCCAGTGCGTGAACCTGACCACCCGGACCCAGCTGCC 131
| type_enthusiast wrote:
| 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?
| plattyp wrote:
| Who would have thought it'd be this simple if
| covid?(dna) block_virus(dna) end
| sp1rit wrote:
| 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?
| rolph wrote:
| DNA uses base pairs [A,T] and [G,C], this code is for a piece
| of DNA,. if you keep a DNA sequence in vials for later use,
| that is much more stable and easier to manipulate, and repair
| when corrupted.
|
| normally RNA in vivo is complexed with protiens that prevent
| RNA from folding, and annealing into structure that is not
| compatible with translation to protien. In the vaccine this
| isnt happening, this is why RNA is hard to work with and the
| vaccine must be kept so cold.
|
| This is not to say that DNA is simple to work with, but it
| solves problems if you dont need direct access to RNA.
| feanaro wrote:
| You probably mean uracil, not udenine (which doesn't exist
| AFAIK).
| koeng wrote:
| 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.
| Laforet wrote:
| The convention of genomic research is to present all RNA
| sequences as equivalent cDNA sequences. As this will be the
| output of most common sequencing platforms.
|
| https://bioinformatics.stackexchange.com/questions/11353/why...
| bvanderveen wrote:
| > .docx.pdf
|
| Cargo-cult much?
| brian_herman wrote:
| https://github.com/brianherman/Assemblies-of-putative-SARS-C... I
| posted some txt files with the lines removed and stuff.
| flobosg wrote:
| If you have the time, it would be nice to transfer the data to
| the commonly used Genbank format.
| brian_herman wrote:
| https://github.com/brianherman/Assemblies-of-putative-
| SARS-C...
| brian_herman wrote:
| Ask and ye shall recieve! Have a great day!
| brian_herman wrote:
| Yeah I'll try.
| kart23 wrote:
| 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?
| iso1337 wrote:
| It's the 3' (3-prime) UTR (un-translated region). It can affect
| the translation of the mRNA.
|
| https://en.wikipedia.org/wiki/Three_prime_untranslated_regio...
| .
|
| The next thing is the poly-A tail:
|
| https://en.wikipedia.org/wiki/Polyadenylation
|
| blasting the 3' UTR, we see it ~50% of it was copied from the
| human mitochondria
|
| tldr, extra regulatory signals (often not well understood)
| [deleted]
| dnautics wrote:
| Doesn't really make sense for it to copy from the
| mitochondrion; I presume this thing gets expressed in the
| cytosol.
| hfjfktmtkrn wrote:
| Among other things that purple region determines the
| "priority"/"intensity" of the whole sequence.
|
| You want it as high as possible to make as much spike protein
| as possible.
|
| It's proprietary information, mostly they try various
| possibilities until they find one with high expression.
| Asparagirl wrote:
| So it's the mRNA version of _!important_ in CSS?
| hfjfktmtkrn wrote:
| More like font-weight, since !important is binary and this
| is more of a gradient.
| _theory_ wrote:
| That's the part that makes you randomly yell, "Hail Bill
| Gates!"
| fabian2k wrote:
| The 3' and 5' untranslated regions are the parts of the mRNA
| directly before and after the part that encodes the actual
| protein. So they are themselves not translated into amino
| acids.
|
| What they actually do can vary, but essentially they can
| provide places for other things to bind and influence what
| happens with the mRNA. There are some fancier cases like
| riboswitches, but you don't see those in humans. The stuff at
| the start and end of the mRNA also determines stability of the
| mRNA.
| flobosg wrote:
| In the BioNTech/Pfizer mRNA, the 3' (or the latter) half of the
| 3'-UTR comes from human mitochondrial 12S rRNA.
|
| The Moderna one has the 3'-UTR of the alpha subunit of human
| hemoglobin.
| layoutIfNeeded wrote:
| That's the copyright notice.
| VectorLock wrote:
| People joked a lot about "injectible source code / machine code"
| but it is kind of interesting injecting yourself with something
| that has the source on github.
| calylex wrote:
| Just because you see the RNA/DNA sequence on Github doesn't
| mean anything, DNA sequencing has been around since at least
| the early 70s [0]. Many pharmaceutical drugs already employ
| such techniques.
|
| [0] https://en.wikipedia.org/wiki/DNA_sequencing#History
| [deleted]
| dnautics wrote:
| Note that this is a sequencing result, so it will lack a lot of
| nonstandard RNA tricks that these companies are or might be
| using, like pseudouridines, or fluorobases. I think those would
| have to be disclosed in the patent.
| vmception wrote:
| We aren't that different from machines, we just need to know
| more about the CPU and all the co-processors and how the logic
| gates interact
|
| But for now we can inject code to trigger protein configuration
| via the immune system
| anyfoo wrote:
| > We aren't that different from machines, we just need to
| know more about the CPU and all the co-processors and how the
| logic gates interact
|
| Except it is unfortunately not that simple, because it
| assumes that distinct components such as CPU, co-processors
| and even logic gates exist in that context, as is totally
| reasonable to assume on devices created by humans.
| Abstracting complex machines into distinct components is a
| proven strategy to engineer a system, but it's not a
| necessity for functioning systems to exist.
|
| In the case of natural organism, they "just" need to work.
| They don't have a blueprint, and they don't need to be
| organized in a way that allows for easy understanding by
| looking at individual parts in separation.
|
| Consider also the difference between machine learning through
| neural networks ("we stuff a lot of training data in there
| and get what we want eventually, we hardly understand what
| the model does or why it fails"), and a QR code reader ("we
| carefully designed the format from the top down, including
| e.g. framing, error correction, and several invariants like
| rotation; if a QR code does not get recognized, we can
| usually tell exactly where and why it failed").
| callesgg wrote:
| It is actually sort of strange how compartmentalized the
| living cell is.
|
| I guess there is some type of redundancy that comes from
| compartmentalization that is evolutionarily beneficial.
| _joel wrote:
| Does that mean a cytokine storm is the equivalent of a buffer
| overflow or a DoS?
| YarickR2 wrote:
| IDS with ability to launch countermeasures, and no negative
| feedback loop
| fabian2k wrote:
| A cytokine storm is when you trick the antivirus into
| thinking all major system files contain a virus.
| Angostura wrote:
| Cytokine storm would perhaps be like the user deleting
| random necessary OS executables in an attempt to get rid of
| malware
| [deleted]
| zappo2938 wrote:
| Wow Looks like it is analogous to having a header on a TCP
| packet. [0] Here is an animation of mRNA encoding translated to
| proteins inside a ribosome. [1]
|
| "The ribosome is composed of one large and one small sub unit
| that assemble around the messenger RNA, which then passes through
| the ribosome like a computer tape. The amino acid building
| blocks, that's the small glowing red molecules, are carried into
| the ribosome attached to specific transfer RNAs; that's the
| larger green molecules also referred to as tRNA. The small sub
| unit of the ribosome positions the mRNA so that it can be read in
| groups of three letters known as a codon."
|
| Very analogous indeed.
|
| [0] https://xerocrypt.wordpress.com/2014/07/22/how-to-read-
| almos...
|
| [1] https://www.youtube.com/watch?v=TfYf_rPWUdY
| retrac wrote:
| Some parts of gene transcription are so straightforward one can
| almost be tricked into thinking it has the logic of a computer
| program. It may be an illusion. To stretch the metaphor, TCP
| parsers don't match probabilistically along the entire length
| of the packet in parallel, and they don't interpret the same
| part of a packet as data in some contexts, and a header in
| others.
| robbiep wrote:
| I ended up majoring in biochemistry and molecular biology in my
| undergrad because I was browsing on Wikipedia one day and came
| across an article written on an E. Coli variant that had
| sentences like:
|
| 01J3 e. Coli has a DNA Polymerase that contains 3k'-5'
| proofreading capability and 5'-3' error correcting with a
| polymerisation rate of 50bps
|
| I've made the above up because I have never been able to find a
| Wikipedia page winxe that as succinctly pointed out to me that
| biology was a machine and I was hooked
| zappo2938 wrote:
| At what point will project managers describe the development
| progress of a project with phrases like "punctuated
| equilibrium?"
|
| Manager: We haven't had a release in 2 months.
|
| Developer: It is period of punctuated equilibrium.
| jturolla wrote:
| Please someone... create some abstraction language for this bio-
| assembly code. Can we make LLVM compile this? :joy:
| ur-whale wrote:
| 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 place? Do the
| coronaviruses use m-RNA as well? Was then a coronavirus somehow
| "dissected" to get at the spike protein "source code"?
| flobosg wrote:
| 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.
| koeng wrote:
| 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.
| ur-whale wrote:
| Thanks !
| [deleted]
| azernik wrote:
| a) I don't know if protein-folding software is good enough to
| figure out the exact structure of the resulting protein given
| just the gene, but I suspect you could figure out through the
| equivalent of the strings command - looking for sub-chains of
| the protein, and looking for matching sequences in the gene
|
| b) Coronaviruses happen to be RNA viruses; that is, their
| genomes are RNA rather than DNA. There are also DNA viruses. We
| got full genomes from sequencing very very early, and continue
| to use it to monitor the evolution of the virus (see e.g. [1],
| where the results are available for download). Sequencing is
| very cheap and easy these days - you take a sample from a
| patient, use chemicals to break down all the cell membranes and
| such, sequence all of the DNA and RNA in it, and look through
| the results for a virus genome (i.e. something that isn't a
| human chromosome and isn't a known virus or bacterial genome).
| "m"RNA is more a description of the function than the chemical
| - tRNA and rRNA are short snippets of RNA used for
| manufacturing purposes inside the cell, while mRNA is the long
| chunks that actually carry information from the DNA to the
| protein manufacturing sites. Virus RNA basically functions as
| imposter mRNA, getting those manufacturing systems to make more
| viruses.
|
| [1] https://www.ncbi.nlm.nih.gov/datasets/coronavirus/genomes/
| - SARS-CoV-2 is the COVID-19 virus. As of my fetch, there are
| 71,509 full sequences of the virus, reflecting slight mutations
| over time and space.
| wonderwonder wrote:
| We are simply programmable machines, its pretty interesting that
| all of human life can be reduced down to 30k editable
| microservices.
| 8note wrote:
| That gives me the feeling that those reflexion models could do
| some help for improving our understanding of those
| microservices
| flobosg wrote:
| > So how different is the mRNA in the Moderna, BioNTech/Pfizer &
| CureVac vaccines? There are 1274 codon positions. 808 are
| identical across all 3 vaccines. 103 are unique to Moderna, 249
| unique to BioNTech, 230 to CureVac
|
| https://twitter.com/PowerDNS_Bert/status/1375091898797453326
| savrajsingh wrote:
| My question is do the other vaccines (pfizer & jnj) encode for
| the exact same spike protein, or a different one they chose to
| target?
| elliekelly wrote:
| I'm a little confused by the title? Looking at the document, it
| seems to me (and knowing next to nothing about this field) it
| includes both Pfizer and Moderna's protein spike sequence in
| figures 1 and 2, respectively. Is that correct?
|
| It's also interesting the way it's worded: that the sequence was
| "assembled from $vaccine". Does that mean whoever published this
| has backed into these sequences rather than having gathered this
| information directly from the source(s)?
| hfjfktmtkrn wrote:
| They sequenced vaccine leftover remaining in used vials.
|
| So reverse engineering basically.
| flobosg wrote:
| The authors reverse engineered the sequences of the vaccines,
| obtaining them from the remaining mRNA present in the vials.
|
| "Assembly" in this case means that they merged several short
| sequences they obtained, each representing a fragment of the
| whole mRNA sequence.
| phcordner wrote:
| You are correct. The researchers here sequenced each vaccine
| starting with the bit of vaccine left in the vial after
| administration. The goal was to get a raw sequence of the
| Moderna mRNA component so it can be easily filtered out as
| being a signal of therapeutic origin. Pfizer's sequence has
| already been published; it's incldued here to confirm that the
| result achieved experimentally matches the published sequence.
| yrral wrote:
| Related: Here's a article from late last year describing and
| explaining the source code of Pfizer vaccine:
|
| https://berthub.eu/articles/posts/reverse-engineering-source...
|
| It's a very interesting read and I hope the author makes another
| post explaining the differences of the two mrna vaccines.
| throwawaysea wrote:
| From that link:
|
| > The injection contains volatile genetic material that
| describes the famous SARS-CoV-2 'Spike' protein. Through clever
| chemical means, the vaccine manages to get this genetic
| material into some of our cells.
|
| > These then dutifully start producing SARS-CoV-2 Spike
| proteins in large enough quantities that our immune system
| springs into action. Confronted with Spike proteins, and
| (importantly) tell-tale signs that cells have been taken over,
| our immune system develops a powerful response against multiple
| aspects of the Spike protein AND the production process.
|
| What happens to the "volatile genetic material" at the end of
| this? Does it just linger in the body indefinitely? Or does it
| somehow get destroyed (and what does that mean)? From my
| reading of the above excerpt, it's the produced spike proteins
| that get destroyed but not the original genetic material that's
| injected. The reason I'm asking is to understand how the
| vaccine designers determine if there are any long-term effects
| of having this artificial material inside your body. They
| couldn't have tested it over a long time frame given how
| quickly all this moved.
| fabian2k wrote:
| The mRNA is stable for a few hours or so, it is both
| chemically unstable in solution under the conditions in a
| cell and also actively degraded by various mechanisms.
| drtz wrote:
| 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.
| azernik wrote:
| 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 patient - and insert it into a human cell.
| (This is called the "platform", and is usually developed
| independently from the specific payload.)
|
| - manufacturing: both producing the mRNA itself at a large
| scale, and inserting it into the delivery mechanism, at a large
| scale and in low-temperature conditions
|
| - 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
|
| EDIT: As schoen pointed out, this was not actually released by
| Moderna, but reverse engineered by third-party researchers.
| Original text was: "Hence they feel safe releasing this. Their
| moat is not the gene sequence, their moat is everything else."
| schoen wrote:
| > Hence they feel safe releasing this. Their moat is not the
| gene sequence, their moat is everything else.
|
| One or more of the vaccine developers may have released such
| details, but this particular file is a reverse engineering
| effort by unaffiliated scientists based on analyzing the
| dregs of used vaccine vials (!).
|
| Edit: See https://news.ycombinator.com/item?id=26628594 for
| more substantive discussion about this.
| azernik wrote:
| Ah - thanks for pointing this out! Edited to make sure
| readers see it.
| wespiser_2018 wrote:
| from what I've gathered, the rate limiting step for
| production as of yet, is creating the lipid vesicles and
| getting the RNA inside of them. Only a few companies have a
| process for this, and the supply chain for the precursors is
| limited as well.
| outworlder wrote:
| > 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.)
|
| Of note, the immune system is pretty good at destroying
| foreign mRNA so you also need to evade it.
|
| This article is pretty good:
| https://berthub.eu/articles/posts/reverse-engineering-
| source...
| purple_ferret wrote:
| 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 x 20 x 20 x 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 10390
| (20300) 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."
| MauranKilom wrote:
| The exponentiation signs got lost in your quote. Would you
| mind adding them back in?
| mattnewton wrote:
| 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.
| flobosg wrote:
| Sequencing technologies have improved immensely over the last
| decade and a half. And, in this particular case, getting the
| sample RNA is incredibly easy, since its purity and integrity
| in the vial is quite high.
| lettergram wrote:
| 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 mechanism for
| injection is developed
| airstrike wrote:
| > and I can easily fit it on my screen.
|
| ...with GATACCA right in the middle, but unfortunately with no
| GATTACA that I could find.
| hfjfktmtkrn wrote:
| It's not really that simple.
|
| Only two companies in the world succeeded, the French company
| Sanofi which also tried making a mRNA vaccine failed.
| WheelsAtLarge wrote:
| True, most pharmaceuticals can't do it now but given the
| right knowledge, which is known, it can be done relatively
| fast. I suspect in the next few years there will be many
| companies that will be able to replicate and advance the
| process.
| fermienrico wrote:
| It's like looking at the binary file and saying "that's
| pretty simple" while ignoring the massive amount of machinery
| that allows us to run that file and use it (CPUs,
| Motherboards, computers, etc).
|
| I presume a whole bunch goes into making vaccine and this is
| just the top of the iceberg.
| puzzlingcaptcha wrote:
| Here is a breakdown https://berthub.eu/articles/posts/reverse-
| engineering-source... discussed previously
| https://news.ycombinator.com/item?id=25538820
| tablespoon wrote:
| > 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 Ps. The
| really clever bit is that although this replacement Ps
| placates (calms) our immune system, it is accepted as a
| normal U by relevant parts of the cell.
|
| Neat.
| WheelsAtLarge wrote:
| No wonders some people have an allergic reaction. Those
| people's immune response is more active to this change.
| lamontcg wrote:
| No they have allergies to the polyethylene glycol PEG
| compound in the lipid nanoparticles. It is also used in
| skin creams, toothpastes, condom lubricants and in larger
| quantities as a laxative. Some people are just allergic
| to it.
| seiferteric wrote:
| Umm, isn't that kind of scary? Like could you create a
| virus with this Ps that our immune system can't fight at
| all?
| carlmr wrote:
| Maybe I'm thinking too simplified here, but wouldn't this
| only work on the first iteration? After all the virus
| would replicate with Us in your cells and then the
| replicas wouldn't have the advantage anymore.
| IgorPartola wrote:
| My exact question when I read that.
| maxerickson wrote:
| It's part of an instruction to cells to make something.
| Viruses replicate by instructing cells to make viruses.
| Our cells don't know how to make Ps, so the replicated
| virus would have the normal instruction.
| seiferteric wrote:
| Thanks, that is reassuring and makes sense.
| jeroenhd wrote:
| As denoted in the linked article [1]:
|
| " Many people have asked, could viruses
| also use the Ps 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 Ps-modified RNA
| replicating with the Ps still in there. "No, Really, mRNA
| Vaccines Are Not Going To Affect Your DNA[2]" is also a
| good read."
|
| As far as I could tell, this would work well for getting
| a synthetic virus into the human body, but without the
| necessary mechanics within our cell, the special Ps
| chemical won't be reproduced by the virus. That'd mean
| the replicated virus would get snatched up by the immune
| system as soon as it'd get released from the cell.
|
| Theoretically, a complex enough RNA string could be used
| to have our cells build the necessary cellular machinery
| to properly reproduce the virus, but that's a kind of
| altering DNA that's a whole different can of worms.
| There's probably cheaper and easier way of defeating the
| immune system, for example by simply "enhancing" ebola or
| HIV to make them more infectious and more resistant to
| our current drugs.
|
| [1]: https://berthub.eu/articles/posts/reverse-
| engineering-source... [2]:
| https://www.deplatformdisease.com/blog/no-really-mrna-
| vaccin...
| randalluk wrote:
| RNA is genetic material, but it encodes instructions to
| make proteins, which form the physical shell of the virus
| crucial to its function. As a very rough analogy, the RNA
| is source code and the proteins are the compiled program.
|
| It's often the protein molecules that the immune system
| learns to recognise and attack.
|
| RNA vaccines work because your body automatically
| translates them into some recognisable part of the viral
| protein, and then develops an immune reaction to that.
|
| If a virus had Ps instead of U in its RNA, it's still
| going to be making the same type of proteins. I can't see
| why it would be more likely to evade an immune response.
| atleta wrote:
| No. For a number of reasons. First of all, the virus uses
| the nucleotides (A, G, T and U, for wich Ps is used as a
| substitute) produced by the attached cell to create a
| copy of it's genome (RNA). The nucleotides are produced
| by the cell, the virus does not instruct the cell to
| produce them. It just tells the cell to produce and
| assemble the proteins AND the RNA.
|
| Second, our immune system doesn't just attack and
| recognize free floating RNA, but the virus itself. And
| different parts of the virus. First and foremost it will
| recognize the surface proteins (like the spike protein)
| because those are the things that it can see while the
| virus is outside of the cell. Also these are the things
| that the infected cells present on their surface (MHC II
| sites, if I'm not mistaken) to the immune system. (As far
| as I can understand, cells _have to_ present the proteins
| they produce to the immune system otherwise they get
| killed. If they produce alien virus proteins that get
| recognized by the immune system, they also get killed.)
|
| Interesting enough, the immune system somehow also
| recognizes the so called nucleocapsid protein, which is
| the one used to wrap the viral RNA _inside_ the virus.
| (But it gets produced by the cells, so I guess they get
| presented on the cell surface so the immune system can
| learn to recognize and counter them.) I didn 't look into
| the details too much, but as far as I can understand it's
| not clear yet how those antibodies (the ones created
| against this protein) work, because antibodies are
| supposed to be used outside of the cells, but the
| nucleocapsids are only present inside the cells and then
| inside the virus.
|
| To sum it up: the immune system is much more complex, has
| several recognition mechanisms, the viral RNA is mostly
| packed into the viruses (or are inside the cells) and the
| viruses don't have any way to produce Ps (or any of the
| other nucleotides).
| schoen wrote:
| In case others don't know this, the reason this is
| abbreviated Ps (psi) is that Ps is the first letter of
| Greek pseudes 'false, lying', the origin of the prefix
| pseudo-.
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