[HN Gopher] Scientist behind Covid-19 mRNA vaccine says her team...
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Scientist behind Covid-19 mRNA vaccine says her team's next target
is cancer
Author : srameshc
Score : 82 points
Date : 2021-03-19 19:01 UTC (3 hours ago)
(HTM) web link (www.cbc.ca)
(TXT) w3m dump (www.cbc.ca)
| miklosme wrote:
| > The vaccine (...) uses messenger RNA, or mRNA, to carry
| instructions into the human body for making proteins that prime
| it to attack a specific virus.
|
| I love how this technology turns a medical challenges into a
| software problem. Being able to code medicine will open up an
| affordable way to personalized drugs, instead of the current day
| "one size fits all" solutions. What a time to be alive!
| dragontamer wrote:
| I mean, in theory that's possible.
|
| But in practice: personalized medicine is impossible to tests.
| We rely upon giving tens of thousands of volunteers medicine
| ahead-of-time to prove if medicine is safe.
|
| While the technology theoretically exists to make and
| distribute personalized medicine, the ethics and safety
| questions of doing so remain unanswered.
| ghc wrote:
| Personalized medicine has been tested for years in clinical
| trials. Trials require tens -- not tens-of-thousands -- of
| volunteers.
|
| Personalized therapies are being used to treat cancer
| patients right now, and using machine learning to find the
| right binding site for a particular patient's tumor should
| present no more ethical questions than giving them NSAIDs.
| amelius wrote:
| Uhm yeah, but it also opens up ways for hackers to code all
| sorts of biological stuff and put it in our bodies. All from
| behind their keyboards.
|
| Imagine "if dna.get_race() == $RACE then kill();"
|
| Or how about some biological ransomware?
| dragontamer wrote:
| That's really not how mRNA works. If DNA is the source code
| of our body, then mRNA is the machine code that exists in
| L1-instruction cache. (There's another process out there that
| copies DNA into more readily processable RNA)
|
| The way any of this mRNA stuff works is by throwing
| instructions into our body to create certain proteins in
| certain configurations. For COVID19, the vaccine is... as
| XKCD-put it... a set of blueprints to build a "fake death
| star" without any weapons activated.
|
| https://xkcd.com/2425/
|
| ------------
|
| mRNA further has a "innate safety" mechanism, in that it
| degenerates. That's why our body uses DNA after all: because
| DNA does not degenerate, even though RNA is what's actually
| executing so to speak.
|
| So any mRNA medicine will have to be strictly temporary, and
| get its job done in a limited timeframe. The COVID19 virus
| gets around this fact by self-replicating. The instructions
| that our cells execute are to create a new COVID19 virus. The
| original "quine", COVID19 (and all viruses) "print
| themselves" as part of their execution.
|
| -------------
|
| The "vaccine" is a set of blueprints for the COVID19 "spike
| protein" (and ONLY the spike-protein). Since it is missing
| all the other parts of COVID19, it cannot self-replicate. Our
| body then gets trained on recognizing the COVID19 spike
| protein, and is ready when the real thing attacks our body.
| prox wrote:
| I believe there are also viruses who can insert themselves
| into the cells DNA, and there are some articles on how some
| parts of human DNA is already old virus genome. Viruses are
| far more dangerous in that regard.
| dragontamer wrote:
| There's both DNA viruses and RNA viruses. RNA viruses are
| way more common though.
|
| > [DNA] Viruses are far more dangerous in that regard.
|
| Not necessarily. "Corrupt DNA" can be somewhat detected
| the body as a cancer cell. Our "Natural Killer" cells
| then kill those cells.
|
| Cancer / corrupted DNA happens all the time in our
| bodies. Even healthy bodies (!!). The difference between
| a cancer-patient and us however, is that a cancer-patient
| is overrun with cancer-cells.
|
| Our bodies naturally kill off cancer under normal
| circumstances. Figuring out why cancer / corrupted DNA
| completely takes over the body is a big mystery,
| especially because our body is so good at fighting off
| cancer under normal conditions.
| tibbydudeza wrote:
| DNA = X86 opcodes RNA = UOPS/ROPS
| therein wrote:
| A better analogy would be anonymous functions thrown into
| the global namespace that get called with whatever
| arguments that may happen to be on the stack at that
| moment.
| amelius wrote:
| > then mRNA is the machine code that exists in
| L1-instruction cache
|
| But we all know that once an attacker has write-access to
| the machine code in the cache, all is lost ...
| dragontamer wrote:
| I mean, my point is that "if (race == whatever)" is
| completely nonsensical from an mRNA perspective.
|
| There's no way for mRNA to scan the rest of your DNA
| sequence to make an if/else determination. mRNA is just
| gonna execute once its in the body.
|
| > Or how about some biological ransomware?
|
| Yeah, that's called a poison and antidote / antitoxin.
| You don't need mRNA for that. Poison someone's food, and
| as they lie dying, you can offer them the antidote in
| exchange for something.
| amelius wrote:
| > I mean, my point is that "if (race == whatever)" is
| completely nonsensical from an mRNA perspective.
|
| Is it? mRNA can code for a protein that detects other
| mRNA in the same cell, which may reflect any genetic
| characteristic of the host.
| dragontamer wrote:
| mRNA isn't really code. Its a blueprint.
|
| https://www.nature.com/scitable/topicpage/translation-
| dna-to...
|
| When we say mRNA "executes", that's a cell injesting
| mRNA, and assembling a protein (polypeptide). For
| example, the mRNA sequence 'ACU', when 'executed' by a
| cell, will turn into a Threonine:
| https://en.wikipedia.org/wiki/Threonine
| Dylan16807 wrote:
| RNA can fold up and get stuck to other sequences. Using
| that as a trigger isn't out of the question.
| monocasa wrote:
| I don't quite follow. The whole shtick with problem cancers is
| that your immune system is ignoring them for whatever reason.
| mRNA vaccines work by priming the immune system for something it
| would attack anyway, but under safer circumstances since there's
| no real virus in the vaccine. What can the mRNA create that the
| immune system will train on given that the immune system isn't
| attacking the real thing to begin with?
|
| (And to be clear, this obviously is a piece I'm missing rather
| than a hole I'm trying to punch in their work. They're way
| smarter than me and wouldn't be working on this unless they had a
| clear idea)
| mushishi wrote:
| Just a newbie question: Would it be beneficial that body itself
| generates transcriptional repressor proteins (via mRNA vaccine)
| that bind to specific cancerous mutation genes instead of
| giving some medicine that has similar inhibitory goals?
|
| (Sorry, I'm just trying to learn cell biology on my own.)
| rolph wrote:
| it is difficult enough to target a cell and deliver to the
| cytoplasm, when you attempt to move further and deliver to
| the nucleus this is further difficulty. if you are certain
| you have a _specificly_ targeted delivery that stays away
| from non cancerous cells you can use mRNA to create labels
| [antigens] on the cell surface that the immune system
| interprets as pathogenic, thus immuno targeting oncocytes for
| destruction.
| azinman2 wrote:
| I don't know the biology, but mRNA vaccines has been used for
| cancer for some years now. I wish this message was louder and
| clearer because people seem to think covid is the first use of
| the technology.
| Slimbo wrote:
| My very basic understanding is you customise the mRNA payload
| towards the immune system targetting the mutating cells that
| have caused cancer in a patient (after the cancer material has
| been surgically removed). This prevents the cancer from re-
| occuring.
| monocasa wrote:
| Right, but the immune system already wasn't responding to the
| mutated cells, and was obviously exposed to any proteins that
| would identify them.
| rolph wrote:
| commented up thread a couple posts:
|
| https://news.ycombinator.com/item?id=26518258
| IfOnlyYouKnew wrote:
| I believe the advantage of the mRNA method is that it's
| somewhat generic: you can stick any (protein-coding) RNA
| fragment into it, and it will be expressed in the body and
| picked up as a target by the immune system if it has any
| potential for the latter (I. e. isn't something that's
| ubiquitous in the body already)
|
| As such, it is faster to get from idea to vaccine. Recent
| history is an example already, but the cycle will be improved
| dramatically considering the technology is very much still in
| infancy. It's also cheaper, to the point that producing ten
| doses of ten different vaccines may not be more expensive than
| producing a hundred doses of a single vaccine. This will be
| helpful against "cancer" which is closer to an unlimited number
| of different diseases than a single target.
| arrosenberg wrote:
| It sounds like you are conflating the antiviral implementation
| with what the mRNA technology itself is doing. mRNA acts as a
| blueprint for proteins. Your body has tRNA translation
| complexes that "read" the mRNA and appropriate the correct
| amino acid to add to the protein chain. Here is a more detailed
| description - translation begins about halfway down with the
| UGCAs: https://www.nature.com/scitable/topicpage/translation-
| dna-to...
|
| So basically the mRNA tech is a means of delivering protein
| blueprints for in vivo production using your bodies natural
| machinery. In the case of COVID-19, this was used to
| manufacture spike protein, which attracts the body's immune
| response.
|
| I'm not an expert on the best way to use the tech with cancer,
| but I could imagine a number of different approaches - targeted
| inducing of cell death, "painting the target" for chemo drugs,
| making things like monoclonal (designer) antibodies in-vivo,
| etc. The silver bullet is that it eliminates all of the
| complexity of creating and storing advanced biologics outside
| the body. Now you just deliver a bit of code and your body does
| it's thing.
| rickdeveloper wrote:
| > the correct protein to add to the chain.
|
| Slight error: it adds an amino acid to the chain. The chain
| itself is/will fold into a protein.
| arrosenberg wrote:
| That is true, thanks for the correction.
| adrianmonk wrote:
| > _I could imagine a number of different approaches -
| targeted inducing of cell death, "painting the target" for
| chemo drugs, making things like monoclonal (designer)
| antibodies in-vivo, etc._
|
| The article does explicitly call it a "cancer vaccine"
| (direct quote from the researcher) and says "the same
| principle [as the COVID-19 vaccine] can be applied to get the
| immune system to take on tumours".
|
| That's more specific than sneaking in with mRNA to get the
| body to produce something. It definitely sounds like whatever
| it is, it gets the immune system involved. It seems fair to
| ask exactly how it does this.
| snowwrestler wrote:
| Scientists are already showing some promising results using
| the immune system against tumors. See for example:
|
| https://en.m.wikipedia.org/wiki/Pembrolizumab
|
| The promise of mRNA is the potential to prompt the body to
| produce the therapeutic antibodies itself, rather than
| produce them externally and injecting regularly.
| rolph wrote:
| off the top of my head:
|
| cancer cells have distinctive traits that can be exploited for
| targeting [1]. A fairly elegant approach is to use a vesicle
| studded with antibodies to the tumor antigen to get the payload
| to the bad cells, the mRNA is then endocytosed into the tumor
| cell, expressed and the protien product adorns the tumor cell.
| when this is an antigen such one sees with measles there would
| be a long lasting immune response that would look for any cells
| with this antigen [i.e. target tumor cells]
|
| [1] https://en.wikipedia.org/wiki/Tumor_antigen
| ergljlkegrwlj wrote:
| Covid "scientists" are quacks and conspiracy theorists. Why don't
| you all go back to your fake moon landings and flat earth
| theories - leave the rest of us alone.
| chiefalchemist wrote:
| > The scientist who won the race to deliver the first widely used
| coronavirus vaccine says people can rest assured the shots are
| safe,
|
| Ok. But did anyone expect her to say anything else?
|
| This is obviously a (slightly?) veiled pitch for backers, more
| funding, and perhaps some regulatory freedom.
|
| It's unfortunate that the media can't resist the temptation to
| pitch this as news. It's not. It's interesting. There's certainly
| intrigue at 50k ft. But you don't ask the cow, "What do you think
| of milk?"
|
| Promise and hope should be tempered with context. We've been to
| this rodeo before.
| vibrio wrote:
| "next target"? has been a target since inception. At Moderna or
| BioNtech Cancer and Gene Therapy were priorities during the last
| decade or so, with limited evidence of success as far as I can
| tell. Infectious disease is scientific low hanging fruit for this
| approach, but has been less attractive commercial opportunities,
| so received limited focus on that until SARS-COV-2. The did a
| good job executing on the vaccines, but I'm not giving much for
| these vaccines as proof of concept for scientific success in
| cancer or orphan disease gene therapy.
| bryanlarsen wrote:
| > so received limited focus on that until SARS-COV-2
|
| Or more accurately, until Bill Gates invested and retargeted
| them at vaccines. These investments predated Covid19 and were
| in 2015 and 2019.
| thepangolino wrote:
| I'm pretty sure the SARS-CoV-2 mRNA vaccines are based on
| mRNA vaccine research for the original SARS virus. The only
| reason that one wasn't finalised is that the epidemic sort of
| died out on its own.
| [deleted]
| xiphias2 wrote:
| The time that mRNA vaccines will save compared to the effort
| people had to do to optimize data to fit in an adenovirus
| vaccine in itself can speed up science significantly.
|
| About 50-100 different sicknesses are being targeted right now
| (a lot of them in secret), so we can't know the biggest winners
| yet.
| jfengel wrote:
| Now that it's been proven and the manufacturing scaled, there
| may be a fair bit of profit in it. If tuberculosis, MRSA, and
| even malaria can be targets, that would be world-changing.
|
| I'm not even sure how "cancer" is really a target -- are they
| talking about individualized treatments for your specific
| cancer cells?
| jl2718 wrote:
| The process generally relies on discovery of potent
| neoantigens within the somatic mutations and then building
| mRNA to express it. So, yes, the idea is individualized
| treatment for cancer. I'm not sure there is any relevance for
| organism-scale immunity like TB/MRSA/malaria.
| JediPig wrote:
| I would first want it to work without side effects and give it
| time to study. The vaccine is less effective than sputnik
| vaccine. Given a choice, I would take sputnik 100 times over.
| tibbydudeza wrote:
| It was done before when they used a inactivated HIV virus to cure
| a child with leukemia by reprogramming her T cells.
|
| She was in the terminal stage of disease so hence the approval of
| the experimental treatment , we don't know the long term effects
| or why it did not work consistently in other patients.
| AngryData wrote:
| What? That is like saying your next target after repairing your
| Corolla is the US economy.
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