18 ms·

What can mRNA treat next?

303 points by elsewhen 5y ago

GEBBL 5y ago
I am so excited for the prospect of mRNA treatments, especially in the field of auto immune conditions like multiple sclerosis. Those scientists are heroes.
- jcims 5y ago
  If that's possible, curing type 1 diabetes would be on the horizon as well. There's some evidence that people with t1d have latent beta cells that could be reactivated to restore normal(ish?) insulin response. That would be incredible.
  - vallard 5y ago
    I really really hope so.
- mvanaltvorst 5y ago
  Are there any online resources where I could learn more about what mRNA treatments could theoretically cure? Take Hashimoto's disease for example, a disease where your thyroid gland slowly gets destroyed by your immune system. If I understand correctly, mRNA could stop your thyroid gland from getting destroyed in the first place, but it cannot regenerate the thyroid gland if it has already been destroyed. Is that correct?
  - henron 5y ago
    My mental model is that in the next decade or so mRNA treatments could be effective if a disease can be treated through the expression of a small number of proteins. These proteins could either have a direct function or stimulate an immune response. I think your example works.
    - mvanaltvorst 5y ago
      What kind of proteins are important when you're looking at the immune system? Is there a protein that can attach to thyroid gland cells and signals to the body that it isn't a threat? Or is there some sort of memory of the immune system with non-threat cells, that mRNA could overwrite? I'm not a biologist, I'd love to read more about these specific inner workings without dissecting a whole undergraduate biology book.
- pseudosudoer 5y ago
  I haven't read anything related to treating autoimmune diseases with mRNA, that would be quite exciting. Do you happen to have a reference for this? I have Ulcerative Colitis, which is a form of an autoimmune disease. A vaccine as a cure would be a game changer.
  - azinman2 5y ago
    But I thought we don’t really know what causes UC. Fungi? Bacteria? Genetic factors? Something else?
    - pseudosudoer 5y ago
      You're correct, doctors/biologists still do not know the root cause of IBD (UC/Chrons). In fact, most autoimmune diseases are quite poorly understood due to the vast dimensional space that can influence the human immune system. If there is evidence that it could be controlled via an mRNA vaccine, it would give me much hope for the future of controlling autoimmune diseases without consistent drug intervention or surgery.
  - sapsan 5y ago
    Maybe something like that is relevant: https://science.sciencemag.org/content/371/6525/145 https://science.sciencemag.org/content/371/6525/145. There's also a bit more context here: https://www.nature.com/articles/s41587-021-00880-0 https://www.nature.com/articles/s41587-021-00880-0.
- usrusr 5y ago
  How would the treating of auto immune work? In my understanding you can trick the immune system into putting yet anther protein on the "kill on sight" list, by forcing the protein's mRNA blueprints into the production pipeline of some cells and... waiting, assuming that the immune system does its thing. So far so good. But isn't an autoimmune problem an entry on the "kill list" that shouldn't be there? I understand how we can append to that list (through a fascinatingly elaborate stack of indirections), but how can we revoke an entry? Not questioning, just willing to learn.
  - IAmGraydon 5y ago
    https://khn.org/morning-breakout/biontech-reports-breakthrough-in-treating-multiple-sclerosis-with-another-mrna-vaccine/ https://khn.org/morning-breakout/biontech-reports-breakthrou...
    - jonlucc 5y ago
      I work in a pharma company, and I have been working with the animal model they use for this paper regularly for the past 4 or 5 years. I am not an mRNA therapy expert by any means, so I'll only comment on the results from the MOG35-55 and PLP EAE models. They have good disease induction in their control groups, their targeted mRNA therapy shows pretty remarkable efficacy, and they show they can diversify a little bit with respect to the target. These models are a little too "furry test tube" for me for this application. They work by injecting an antigen, either a short version of the myelin oligodendrocyte glycoprotein (MOG) peptide or the myelin proteolipid protein (PLP). The mouse makes antibodies against that antigen, and those antibodies also attack those antigens in their natural environments, leading to demyelination in the CNS. Well their mRNA for the MOG model makes more MOG peptide, giving the antibodies another target so they don't cause demyelination. In the human condition, there are multiple antibodies against multiple targets, so I'm not sure this is as relevant as they're suggesting, unless I'm missing something. I do want to add that this paper has a ton of work in it, and it looks pretty high quality as far as I can tell. None of this is to say there's no value here, I'm just not sure what target they would make an mRNA for to treat human MS based on this paper or how they'd identify and test that target to get FDA approval to move into trials.
bsanr2 5y ago
Hopefully my height. Hello, 6 feet.
- CoastalCoder 5y ago
  Probably a niche application. Most persons want exactly two.
  - danthedan 5y ago
    this isn’t reddit
  - valarauko 5y ago
    True, though most people also have more than the average number of feet.
  - bsanr2 5y ago
    I dunno. The confluence of the interests of furries and Metal Gear/Deus Ex/Cyberpunk fans might make for a lucrative market leading into the widespread adoption of Anansization. Jokes aside, I'm surprised at the rather negative response. As a medical problem, you're looking at not just cosmetic applications, but also treatments for not-uncommon disfigurement or injury, and the phasing out of existing, quite brutal, leg-lengthening surgeries. Philosophically, you have the issue of bodily agency, and the opportunity to remove that particular source of interpersonal disparity and discontent. Scientifically, I'd think it an interesting problem, one that seemed as implacable as death, except that it isn't, because we have brute-force methods to circumvent the proscriptions of the natural process. Figured that would be something HN would be eager to chat about.
intricatedetail 5y ago
I would love that the state sponsored research into chronic pain. Big pharma has no incentive to find cure, they want to push a suite of addictive pills that ruin lives or they spend money to block medical cannabis. Millions of people suffer with no way out. Edit: why people downvote the truth? I guess none of you suffered this and I hope you will not, but silencing a voice like that is inhumane.
- Steuard 5y ago
  I didn't downvote, but if I had to guess, I suspect it's because your comment seems to have very little to do with the article (apart from the fact that the article is about medical research and you are advocating for a different sort of medical research). If there's a specific reason to think that mRNA could be used in treating chronic pain, including that could make your comment more obviously on-topic. (Not that your underlying point is a bad one! It's just hard to see how it fits in a discussion of this particular article.)
- dcminter 5y ago
  Probably because it's not really on topic. Worth reviewing the site guidelines here: https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
- cigaser 5y ago
  Chronic pain is just a symptom. There could be million causes that needs to be treated first. And cannabis is just another form of "addictive pill", no better than opioids.
- perardi 5y ago
  Well…there is state sponsorship, via the NIH. https://www.nccih.nih.gov/nih-pain-research-center/research-projects https://www.nccih.nih.gov/nih-pain-research-center/research-... “Pain” is almost never the disease. (OK, maybe CRPS.) There’s a lot of things that cause pain, almost self-evidently, so it’s not one particular thing to attack, unlike a virus. (Also we are at 36 states now with medical marijuana, so I think the “pharma wants to block this” ship has sailed, especially when you consider big-hitters like California and New York have full recreational marijuana now.)
Steuard 5y ago
It's an indictment of something that we've had this amazing new tool for vaccine production in existence for a decade but we never even tried to use it for that until COVID because "vaccines typically don’t make much money" and "vaccines just aren’t that exciting" scientifically: "it’s nice and easy," to quote Rossi from the article. If it really does turn out that effective mRNA vaccines can be created in a straightforward way for a host of new diseases, that's ten years of deaths and misery that we as a society just allowed to happen unnecessarily. I don't know how to fix that: maybe the market-based incentive structures that work for acute disease treatments aren't a good fit for broad preventative public health measures like vaccines.
- mchusma 5y ago
  Or focus on lowering costs. We learned in the pandemic how fundamentally broken the FDA is. There is no reason that things can't be faster that "operation warp speed" all the time. Or re-focus the monetary models around either markets or patient outcomes. Right now, medicine is not a market, it's a strange game. The most money that can be made is finding a treatment that may provide a modest increased benefit over what is live, then sell it to medicare at "name your own price". This incentives high probability wins (which are typically things we already understand well).
  - Ericson2314 5y ago
    By this model vaccines are sadly "too effective" on two counts: - They are preventative. Americans are scared that regular people walk into hospitals and debt peons walk out. We are too sickly and scared for preventative medicine, and like our infrastructure which is never maintained to the point of being in "good working order". - They are O(1) dose. The unity economics of once-and-done is bad. Better to sell something which makes a customer for life. It's really depressing.
  - azinman2 5y ago
    > There is no reason that things can't be faster that "operation warp speed" all the time. Because money. Operation warp speed started mass manufacturing at the same time as clinical trials. 70% of drugs fail the 3rd stage of trials, so that would be a hugely wasteful endeavor to parallelize this when failure is the norm.
jcims 5y ago
Many cancers exhibit immunosuppressive qualities that allow them to co-exist in a healthy immune system. It seems possible that mRNA-based therapies could be used to interfere with those mechanisms (eg binding to PD-L1, etc). The delivery mechanism for the mRNA appears to be the primary innovation and I wonder if it would be possible to target it at specific cells. In the cancer context if you could differentially target the mRNA delivery to cancerous tissue, the 'payload' could be more generally cytotoxic but only affect tissue proximate to cancer cells. This seems like it's on the order of CRISPR for potential to change the landscape of medicine in the next 50 years.
- umanwizard 5y ago
  Possibly naive question: if you can differentially target any particular thing to cancer cells specifically, why not just deliver poison to kill the cells directly? I.e. chemotherapy but without any of the nasty side effects.
  - jcims 5y ago
    Not naive at all. I didn't word my question well as my interest is broadly if this new technology gives us any more ability to differentiate the delivery, either by selecting for cancer cells or by only 'activating' within cells that are cancerous. In general there are a number of 'targeted' therapies being developed that don't specifically target the cancer cell, but try to make life more difficult for the cancer by broadly impacting a cell's ability to hide, replicate and accumulate...features that the rest of a healthy human tissue is less dependent upon.
  - wgolsen 5y ago
    One version of what you are describing is called an antibody-drug conjugate. There are about a dozen ADCs approved and many more in various stages of development
  - 8note 5y ago
    I'd prefer to have the poison not have to be in the same process as the detection? The detector likely needs to enter or interact with the cell regardless of whether it's cancerous
dukeofdoom 5y ago
hair loss?
- Xenoamorphous 5y ago
  I know it’s maybe pure vanity and I definitely wish to see cancer cured first but I think the psychological impact of hair loss, especially in young people (<25), is often underestimated.
  - thijsvandien 5y ago
    I think you can easily make that <45 in case of men, and don't forget about women.
  - rocgf 5y ago
    For better or worse, it's not the importance of a disease per se that drives innovation, it's money. So assuming that hair loss is the kind of problem that would get people to spend money, then we might see some progress here.
    - lazide 5y ago
      There are many possible ways to quantify importance? And many many stakeholders with often conflicting ideas, demands, and influence. If someone is spending money on something, they are voting that it is important FOR THEM - and more important than whatever else they would have done with the money. If politicians/government aren’t spending money on something - despite saying it’s important - that is a very clear signal that their words and their actions do not align. We have words for that too. If they don’t even bother saying words about it, then that is a clear signal not enough pressure is being applied to make it even a pretend priority no?
  - fma 5y ago
    I don't have experience in this field...but w/ hair, someone can get grafts which supposedly look better than plugs from decades ago?
rossmohax 5y ago
Why this article is so Rossi centered? Did he play key role in mRNA breakthrough?
- khendron 5y ago
  Because the article is about him and the company he (co)founded.
- caturopath 5y ago
  Because he/his company is the subject of the article? The headline doesn't make that all that clear, but everything about the article seems to.
ppf 5y ago
The next Covid-19 variant?
- perardi 5y ago
  At the risk of responding to a throw-away comment: https://www.technologyreview.com/2021/01/13/1016098/moderna-variant-coronavirus-vaccine-update/ https://www.technologyreview.com/2021/01/13/1016098/moderna-... They can retool very, very quickly. The slight unknown is running another trial.
coldcode 5y ago
mRNA seems almost like a biological programming language; if you can determine how to build a protein that triggers the body's immune system to attack something you want to destroy it's just a matter of design and testing. I wonder if you could build a real language that you could use to design a sequence and automate the testing.
- deleted 5y ago
  [deleted]
- arrosenberg 5y ago
  You could, but keep in mind mRNA occurs in 3D and thermodynamic and kinetic forces play a huge role in biochemistry, so it’s quite a bit more complicated than your average program.
  - inglor_cz 5y ago
    Well, that is why it comes 50 years later than, say, Kernighan and Ritchie standard of C. The know-how and hardware of today are just enough for the 1.0 of mRNA vaccines, so to say. How will the fourth or fifth generation look like, is probably beyond our imagination right now.
- bqmjjx0kac 5y ago
  Not quite what you're asking for, but check out CRN++ [0], a programming language built on chemical reaction networks (CRN). [0]: https://arxiv.org/abs/1809.07430 https://arxiv.org/abs/1809.07430
- dehrmann 5y ago
  I still find describing anything in biology as a "programming language" to be a bit generous. It still feels more like fiddling with inputs to an ML model.
ProjectArcturis 5y ago
There are a lot of folks excited about mRNA as a "programming language" for the body. And it kind of is, but it's more complicated than that. The critical thing is that mRNA is extremely immunogenic -- that is, it provokes a strong immune response. Makes sense, since evolutionarily when we had little particles delivering RNA strands to our cells, they we viruses. So, that's great for vaccine production. Not so great for other diseases. Cystic fibrosis, for example, the body fails to make one specific protein. We (probably) can't just program it to produce that protein, because it would also train the immune system to target that protein. The best non-vaccine targets are probably cancer, where you want to get the immune system revved up against a tumor.
- im3w1l 5y ago
  What about hiv?
  - simcop2387 5y ago
    HIV is a virus, so it would seem to be a good candidate for mRNA since you'd want to make it generate an aggressive and early response to the virus. I can't even guess though what challenges would arise given that HIV likes to target the immune system itself.
    - unnouinceput 5y ago
      This might shed some light: https://www.businessinsider.com/new-hiv-vaccine-could-be-moderna-mrna-success-story-2021-4 https://www.businessinsider.com/new-hiv-vaccine-could-be-mod...
- CorrectHorseBat 5y ago
  I thought they solved that by replacing U by 1-methyl-3'-pseudouridylyl in mRNA vaccines? I can imagine it's not great for vaccines either, you want the immune system attack the spike the mRNA codes for, not destroy the mRNA before it can do it's thing. https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
ecedeno 5y ago
Moderna has a public development pipeline. It shows they are working on, among other things, an HIV vaccine and vaccines/therapies for multiple types of cancer. https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline
- deleted 5y ago
  [deleted]
- est31 5y ago
  Plus a flu vaccine: > mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [...] > One limitation of the current flu vaccines is that they take about six months to develop, meaning scientists must choose which strains they think will be prevalent in the next flu season — even before the current one is over. So by the time the vaccines are ready for distribution, a different strain may have emerged as the better target. > An mRNA flu vaccine, on the other hand, can be developed in about a month or so, giving researchers much more time to determine which strains to protect against. https://www.washingtonpost.com/health/2021/04/11/mrna-flu-shots/ https://www.washingtonpost.com/health/2021/04/11/mrna-flu-sh... The flu vaccine seems to me to have a better chance of working than an HIV vaccine because we have been trying for decades to come up with one for HIV, without any success at all. I'm not saying that their attempts won't work either, but it's more of a bet than a flu vaccine. An iterative improvement on the existing flu vaccines would still be very helpful.
  - lisper 5y ago
    > by the time the vaccines are ready for distribution, a different strain may have emerged as the better target I have never understood this. How many strains are there? I thought there were only like 4 or so. Why don't they just do them all every year?
    - cannaceo 5y ago
      There are subtypes of each. Influenza A and B cause the seasonal flu. The subtypes are named by their hemagglutinin (H) and neuraminidase (N). E.g. H1N1, H5N9, etc.
cigaser 5y ago
Well, it will treat everything. Soon it will be generic technology, accessible to any low-tier lab with "RNA printer". Any country will be able to download medication from internet. And in most places it is impossible to copyright naturally occurring RNA sequence.
subpixel 5y ago
Tick-borne diseases are not all similar but many of them are very, very nasty and Lyme Disease is not the worst of them. I’d love for my kids to be able to play in the weeds and woods with abandon the way I did.
createmyname 5y ago
and rossi thinks this way: "Immortality is not something that that will ever be achievable" well, noted.
lukeschlather 5y ago
Scientifically and medically, vaccines seem extraordinarily exciting as a simple tool that can permanently eliminate problems. Treatments sound very exciting if I were running a business, but scientifically less so. I'm really glad that we've developed these great mRNA vaccines, and I hope that a business drive for recurring revenue doesn't chase people back to merely looking for treatments.
- sk1459 5y ago
  Permanently? I thought the standard of performance has become “reducing symptoms, maybe, we think, we’re not really sure. This is probably safe though”
  - fighterpilot 5y ago
    True for anti-depressants. Evidence is extremely weak and the large majority of the effect in anyone below severe depression is known to be placebo.
- dehrmann 5y ago
  Once drugs go off-patent, the subscription model is a lot less appealing. Even before then, allowing vaccines to sell for $200 per dose (I'm just making up this number) would encourage vaccine production. But you're right that this is an example of markets not doing the right thing, so it might take government, or even insurance company subsidies on vaccine development.
  - rsynnott 5y ago
    That’s not an outlandish number; retail price of the HPV vaccine in developed countries is about 200 euro a dose (though in practice usually paid by health services). They get a lot cheaper once out of patent, of course.
rdlecler1 5y ago
Greenlight Biosciences (one of our portfolio companies) is using RNA as a highly targeted-species-specific pesticide.
- DocTomoe 5y ago
  This honestly is highly concerning - if that can be done for species, the next step could be to target ethnicity. I feel like this is one of those Oppenheimeresque moments in human history.
  - lazide 5y ago
    It’s been tried and done before via chemical and biological methods (if you don’t want to sleep for awhile, check out what has been declassified on THOSE topics and realize that is what they were OK releasing to the public!). The problem of course is that in deploying it, you’ll inevitably kill a bunch of your own - no population is so consistent you won’t kill a bunch of senior leaders who had parents 3 generations ago who were transracial or whatever and lied about it - and it will inevitably turn everyone in the world against you. Even states like NK or Iran need friends, and those friends would have enough casualties from anything like this there is no scenario I can imagine anyone would intentionally release something like that. Doesn’t mean a mad scientist type would cook it up accidentally in the garage, but there are always real world constraints stopping wide spread (physics sometimes, often effectiveness limits or the like).
    - parshua 5y ago
      Why do you bring Iran or NK into this? Let's get it straight: Until now, the only counties who have actually tried genocide on industrial scale, have performed inhumane tests on live subjects of other cultures or used Nukes on civilian targets have been mostly western. Heck, they were literally wiping each other out right until 75 years ago. They are also the ones actively ganging up and invading others TODAY. What delusion suddenly caused you to think it is again 'others' who are trying to wipe you out?
      - 5y ago
hyko 5y ago
Started reading to find the answer, but gave up wading through the hagiography.
2OEH8eoCRo0 5y ago
What can companies do to ease the public's worry about mRNA vaccines? I work with a number of people who will not get an mRNA vaccine until they are better understood.
- dehrmann 5y ago
  Wait 5 years.
- ALittleLight 5y ago
  The answer seems straightforward then. More research to better understand mRNA vaccines and their consequences plus an effort to communicate what is found in a way that is digestible for lay people.
  - tolbish 5y ago
    How much more easily digestible can you get than this? https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different...
    - ALittleLight 5y ago
      I suppose that gets points for being easily digestible, but it is also from a source that has knowingly lied to the public about covid safety in the past year (masks), it doesn't address any specific concerns related to the vaccine, and this document itself is obviously wrong. For example, it calls the vaccine a "a harmless piece" of mRNA when side-effects to the vaccine that are fairly considered harmful (fever, feeling bad, malaise, etc) are well documented and commonly known. If they wanted to do a good job, the information should come from a trustworthy source, it should present the best arguments against the vaccine, and discuss the merits and lack thereof of those arguments. It should genuinely present the risks and the benefits and a good analysis of the tradeoffs. This document clearly falls well short. You can't expect to convince people like this.
r3pl4y 5y ago
#ExplainLikeImFive Could somebody explain to me what a PVC (Personalized Cancer Vaccine) is? Like what is the personalized part in there? Is there really a realistic scenario in which we'll get some regular vaccination and then we'll be cancer free in the future?
- zaphod12 5y ago
  Ok, so cancer is essentially a blanket term for describing that you have a group of cells in your body doing uncontrollable runaway mitosis (replicating themselves). But the thing is that it's caused by hundreds of different mutations to your cells in thousands of combinations. So developing a single way to combat all of this is super hard. But if we can identify your particular set of mutations and train your body to attack cells with those, we can get rid of your cancer and prevent it from returning. There are a few strategies for this and it's how some of the most incredible cancer therapies of the last few years work...those are just only applicable to certain very specific mutations.
  - r3pl4y 5y ago
    Thank you very much
- deleted 5y ago
  [deleted]
throwaway879 5y ago
Do the concerns raised here have any merit? https://osf.io/epr24/ https://osf.io/epr24/
- throwaway879 5y ago
  Why would anyone down-vote a question asking if there is any merit to some concerns raised by a clinical researcher? The target audience is people working on mRNA vaccines who might be able to shed some light.
  - halfjoking 5y ago
    I'm with you. I have no idea why people don't question anything about the capabilities/consequences of this tech.
- throwaway879 5y ago
  To those downvoting: “The most worrisome part, he said, is that antibodies also can make subsequent infections worse, creating so-called antibody-dependent enhancement. Two vaccines — one against a coronavirus in cats and another against dengue, a flavivirus that affects humans — had to be withdrawn because the antibodies they induced caused potentially fatal reactions. If an antibody binds weakly against these viruses or falls to low levels, it can fail to “neutralize” the virus, but instead help it get into cells.” https://news.berkeley.edu/2020/09/09/for-an-effective-covid-vaccine-look-beyond-antibodies-to-t-cells/?fbclid=IwAR2T98YYuKw1FkK4yYUbwpkQTk7hP_WOO-3tqtPY3W_7d3qiPGejex-hlHM https://news.berkeley.edu/2020/09/09/for-an-effective-covid-...
- thewileyone 5y ago
  https://www.pnas.org/content/116/39/19727 https://www.pnas.org/content/116/39/19727
lucb1e 5y ago
Because it's buried in some two thousand words: > helping cells produce tissue to heal from events such as cardiac arrest > beyond simple vaccines [...] mRNA therapeutics might be tailored to instruct a person’s immune system to fight their specific type of cancer, or target protein deficiencies in specific organs, and without the toxic side effects of traditional medications. > “My personal moonshot is snake venom, and antivenoms for snake bites,” he says. [...] “You inject it into a person, and within hours the protein that you wish is being expressed,” he explains. The final product of such research, he imagines, would be an antidote that could work for the most lethal species of a specific area, delivered in a way that can be preserved for long times in very remote areas—for instance, a powder that can be stored for long periods of time and reconstituted quickly. This is literally all the info I found that is actually relevant to the interesting headline. The rest of the article is about this person's career and what funding vaccine companies got in 2020.
- deleted 5y ago
  [deleted]
- cies 5y ago
  Thanks for the TLDR. Based on this I'll not read it.
- prvc 5y ago
  Thank you for the summary. We know we're deep in the weeds when heart disease and cancer are the afterthoughts among candidate diseases to treat.
- spurgu 5y ago
  I think another key takeaway is that mRNA didn't really seem to interest anyone until the pandemic came along.
  - karmelapple 5y ago
    When you say anyone, do you mean anyone with massive funds to finance a big effort with mRNA? Because that would also be wrong. This comment is either just wrong, or at least missing some very important context. There’s a massive amount of research about mRNA. Gene therapy, vaccines, lots more. And there was money already sunk in to have mRNA vaccines at a proof of concept stage before the pandemic. There just never was the urgency to use mRNA in a vaccine until the last 15 months. But mRNA research is all over the place, and not just in vaccines. Source: my life scientist partner Edit: Google search for RNA institute turns up lots of results at universities all over the place: https://www.google.com/search?hl=en&q=institute%20for%20rna%20biology https://www.google.com/search?hl=en&q=institute%20for%20rna%...
lapalmian 5y ago
BioNTech's current development presentation: https://investors.biontech.de/static-files/53947c63-dd5c-44d3-8543-87c1ecad96a1 https://investors.biontech.de/static-files/53947c63-dd5c-44d... CureVac's pipeline can be found here on page 6: https://www.curevac.com/wp-content/uploads/2021/04/20210421-CureVac-Investor-Handout.pdf https://www.curevac.com/wp-content/uploads/2021/04/20210421-...
Sommer 5y ago
Could there be mRNA applicability to food allergy treatments, peanut allergies in particular?
senbarryobama 5y ago
Can they help Parkinson’s?
throwaway879 5y ago
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827936/pdf/vaccines-09-00036.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827936/pdf/vac...
alcuadrado 5y ago
> Derrick Rossi doesn’t quite see it this way, but he kind of saved the world. > > In 2008, he began researching messenger RNA (mRNA), building on the long-ignored work of Hungarian researcher Katalin Karikó What?! Katalin Karikó is an SVP at BioNTech, the lab that created Pfizer's vaccine.
- jonstewart 5y ago
  Yes, and... she was long ignored before that. https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/ https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-... https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-kariko.html https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-k...
tonymet 5y ago
Anyone know the answer to why the treatment failed after 20 years of research and suddenly succeeded ?
da02 5y ago
Isn't it too early to think about mRNA therapies? VAERS data released today showed 118,902 reports of adverse events following COVID vaccines, including 3,544 deaths and 12,619 serious injuries between Dec. 14, 2020 and April 23, 2021: https://childrenshealthdefense.org/defender/vaers-significant-jump-reported-injuries-deaths-after-covid-vaccine/ https://childrenshealthdefense.org/defender/vaers-significan... The Orange County Coroner's office is investigating the death of a woman who died just days after she received her second dose of the Moderna vaccine: https://abc7.com/health/oc-womans-death-after-vaccination-spurs-concern-from-family/10562182/ https://abc7.com/health/oc-womans-death-after-vaccination-sp... Meanwhile: Using a protocol of zinc, hydroxychloroquine or ivermectin and one antibiotic in combination with inhaled budesonide and/or intramuscular dexamethasone... The early ambulatory treatment regimen was associated with estimated 87.6% reduction in hospitalization and 74.9% reduction in death (p<0.0001): https://trialsitenews.com/texas-physician-researchers-case-series-finds-reduction-in-covid-19-hospitalization-by-87-6-death-74-9/ https://trialsitenews.com/texas-physician-researchers-case-s...
- stbtrax 5y ago
  How would an antibiotic help with a viral infection? Might as well start using some essential oils and homeopathy. If that regimen actually worked, we'd probably see it more widely used and studied. They investigate each death reported to VAERS to see if it was actually vaccine related. Given how many millions of doses were given out, and especially to people that were already old or clinging on to life, 3,544 is not unexpected. None of those were directly attributable to the vaccine.
  - da02 5y ago
    Maybe the antibiotic is for Tuberculosis? https://www.cdc.gov/globalhealth/stories/2020/tb-covid.html https://www.cdc.gov/globalhealth/stories/2020/tb-covid.html
- soared 5y ago
  Please don’t play armchair medical researcher. The question you’ve asked is much larger 3 urls, one of which is an investigation into a single event among hundreds of millions of doses. Your third link is not remotely relevant. The article is not discussing covid treatments, but rather the category of vaccine. Zinc isn’t going to cure cancer.
collyw 5y ago
Maybe worth checking the long term effects before forcing these vaccines on other things. https://pubmed.ncbi.nlm.nih.gov/33300001/ https://pubmed.ncbi.nlm.nih.gov/33300001/
Jemm 5y ago
The article totally glosses over Katalin Karikó who really should be getting the credit.
pajko 5y ago
What are the technology's limits? Would it be possible to create mRNA shots to grow more muscle tissue, regrow teeth or lost limbs?
monopoledance 5y ago
Could mRNA injection temporary restore activity for loss-of-function mutations like p53 deletion in cancer? The general, inherent hurdle in cancer treatment is discriminating individualist, misbehaving cells from cooperative, healthy ones. From what I got, p53 isn't not expressed in healthy cells, but rather inactivated. Therefore it may be possible to systemically restore it in all cells, without inducing apoptosis in well-behaving cells. This would be exciting, because it would enable cancer treatment avoiding selection based on cell signature, or "finding a target". Effectively restoring functionality of cell cycle guardians, which will then suicide the cancer cells seems like an attack vector very hard to evade for cancer cells. You wouldn't ask "who is misbehaving?", but rather shortly reign "everybody does as I say, now!". Cancer cells can get rid of all the surface proteins (targeted by immunotherapy) and even gain root acce.. omnipotent stem cell characteristics (game over), they cannot shake the programmatic hallmarks of cancer, without stop being cancer. And the most important feature isn't rabid metabolism (targeted by chemo), but unchecked cell division. Chemo doesn't work well on indolent/non-aggressive cancers, as their metabolic signature is not discriminating. But who cares, if cells lost e.g. the p53 altogether, if we can force the machinery onto them regardless? No need to diff/patch the source, bring the bytecode to the compiler and fix the system until broken for good. All we want is them to "wake up" briefly and take responsibility for the mess they got at hand. (Of course, it wouldn't be possible to flood the body with "activated p53", as that would probably suicide all cells (although it makes for a pretty scifi murder-agent), and the activation itself may offer an escape... until people figure out the whole shop.) * https://en.wikipedia.org/wiki/P53 https://en.wikipedia.org/wiki/P53 * https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer
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303 points by elsewhen 5y ago

I am so excited for the prospect of mRNA treatments, especially in the field of auto immune conditions like multiple sclerosis. Those scientists are heroes.

jcims 5y ago
If that's possible, curing type 1 diabetes would be on the horizon as well. There's some evidence that people with t1d have latent beta cells that could be reactivated to restore normal(ish?) insulin response. That would be incredible.
- vallard 5y ago
  I really really hope so.
mvanaltvorst 5y ago
Are there any online resources where I could learn more about what mRNA treatments could theoretically cure? Take Hashimoto's disease for example, a disease where your thyroid gland slowly gets destroyed by your immune system. If I understand correctly, mRNA could stop your thyroid gland from getting destroyed in the first place, but it cannot regenerate the thyroid gland if it has already been destroyed. Is that correct?
- henron 5y ago
  My mental model is that in the next decade or so mRNA treatments could be effective if a disease can be treated through the expression of a small number of proteins. These proteins could either have a direct function or stimulate an immune response. I think your example works.
  - mvanaltvorst 5y ago
    What kind of proteins are important when you're looking at the immune system? Is there a protein that can attach to thyroid gland cells and signals to the body that it isn't a threat? Or is there some sort of memory of the immune system with non-threat cells, that mRNA could overwrite? I'm not a biologist, I'd love to read more about these specific inner workings without dissecting a whole undergraduate biology book.
pseudosudoer 5y ago
I haven't read anything related to treating autoimmune diseases with mRNA, that would be quite exciting. Do you happen to have a reference for this? I have Ulcerative Colitis, which is a form of an autoimmune disease. A vaccine as a cure would be a game changer.
- azinman2 5y ago
  But I thought we don’t really know what causes UC. Fungi? Bacteria? Genetic factors? Something else?
  - pseudosudoer 5y ago
    You're correct, doctors/biologists still do not know the root cause of IBD (UC/Chrons). In fact, most autoimmune diseases are quite poorly understood due to the vast dimensional space that can influence the human immune system. If there is evidence that it could be controlled via an mRNA vaccine, it would give me much hope for the future of controlling autoimmune diseases without consistent drug intervention or surgery.
- sapsan 5y ago
  Maybe something like that is relevant: https://science.sciencemag.org/content/371/6525/145 https://science.sciencemag.org/content/371/6525/145. There's also a bit more context here: https://www.nature.com/articles/s41587-021-00880-0 https://www.nature.com/articles/s41587-021-00880-0.
usrusr 5y ago
How would the treating of auto immune work? In my understanding you can trick the immune system into putting yet anther protein on the "kill on sight" list, by forcing the protein's mRNA blueprints into the production pipeline of some cells and... waiting, assuming that the immune system does its thing. So far so good. But isn't an autoimmune problem an entry on the "kill list" that shouldn't be there? I understand how we can append to that list (through a fascinatingly elaborate stack of indirections), but how can we revoke an entry? Not questioning, just willing to learn.
- IAmGraydon 5y ago
  https://khn.org/morning-breakout/biontech-reports-breakthrough-in-treating-multiple-sclerosis-with-another-mrna-vaccine/ https://khn.org/morning-breakout/biontech-reports-breakthrou...
  - jonlucc 5y ago
    I work in a pharma company, and I have been working with the animal model they use for this paper regularly for the past 4 or 5 years. I am not an mRNA therapy expert by any means, so I'll only comment on the results from the MOG35-55 and PLP EAE models. They have good disease induction in their control groups, their targeted mRNA therapy shows pretty remarkable efficacy, and they show they can diversify a little bit with respect to the target. These models are a little too "furry test tube" for me for this application. They work by injecting an antigen, either a short version of the myelin oligodendrocyte glycoprotein (MOG) peptide or the myelin proteolipid protein (PLP). The mouse makes antibodies against that antigen, and those antibodies also attack those antigens in their natural environments, leading to demyelination in the CNS. Well their mRNA for the MOG model makes more MOG peptide, giving the antibodies another target so they don't cause demyelination. In the human condition, there are multiple antibodies against multiple targets, so I'm not sure this is as relevant as they're suggesting, unless I'm missing something. I do want to add that this paper has a ton of work in it, and it looks pretty high quality as far as I can tell. None of this is to say there's no value here, I'm just not sure what target they would make an mRNA for to treat human MS based on this paper or how they'd identify and test that target to get FDA approval to move into trials.

bsanr2 5y ago

Hopefully my height. Hello, 6 feet.

CoastalCoder 5y ago
Probably a niche application. Most persons want exactly two.
- danthedan 5y ago
  this isn’t reddit
- valarauko 5y ago
  True, though most people also have more than the average number of feet.
- bsanr2 5y ago
  I dunno. The confluence of the interests of furries and Metal Gear/Deus Ex/Cyberpunk fans might make for a lucrative market leading into the widespread adoption of Anansization. Jokes aside, I'm surprised at the rather negative response. As a medical problem, you're looking at not just cosmetic applications, but also treatments for not-uncommon disfigurement or injury, and the phasing out of existing, quite brutal, leg-lengthening surgeries. Philosophically, you have the issue of bodily agency, and the opportunity to remove that particular source of interpersonal disparity and discontent. Scientifically, I'd think it an interesting problem, one that seemed as implacable as death, except that it isn't, because we have brute-force methods to circumvent the proscriptions of the natural process. Figured that would be something HN would be eager to chat about.

intricatedetail 5y ago

I would love that the state sponsored research into chronic pain. Big pharma has no incentive to find cure, they want to push a suite of addictive pills that ruin lives or they spend money to block medical cannabis. Millions of people suffer with no way out. Edit: why people downvote the truth? I guess none of you suffered this and I hope you will not, but silencing a voice like that is inhumane.

Steuard 5y ago
I didn't downvote, but if I had to guess, I suspect it's because your comment seems to have very little to do with the article (apart from the fact that the article is about medical research and you are advocating for a different sort of medical research). If there's a specific reason to think that mRNA could be used in treating chronic pain, including that could make your comment more obviously on-topic. (Not that your underlying point is a bad one! It's just hard to see how it fits in a discussion of this particular article.)
dcminter 5y ago
Probably because it's not really on topic. Worth reviewing the site guidelines here: https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
cigaser 5y ago
Chronic pain is just a symptom. There could be million causes that needs to be treated first. And cannabis is just another form of "addictive pill", no better than opioids.
perardi 5y ago
Well…there is state sponsorship, via the NIH. https://www.nccih.nih.gov/nih-pain-research-center/research-projects https://www.nccih.nih.gov/nih-pain-research-center/research-... “Pain” is almost never the disease. (OK, maybe CRPS.) There’s a lot of things that cause pain, almost self-evidently, so it’s not one particular thing to attack, unlike a virus. (Also we are at 36 states now with medical marijuana, so I think the “pharma wants to block this” ship has sailed, especially when you consider big-hitters like California and New York have full recreational marijuana now.)

Steuard 5y ago

It's an indictment of something that we've had this amazing new tool for vaccine production in existence for a decade but we never even tried to use it for that until COVID because "vaccines typically don’t make much money" and "vaccines just aren’t that exciting" scientifically: "it’s nice and easy," to quote Rossi from the article. If it really does turn out that effective mRNA vaccines can be created in a straightforward way for a host of new diseases, that's ten years of deaths and misery that we as a society just allowed to happen unnecessarily. I don't know how to fix that: maybe the market-based incentive structures that work for acute disease treatments aren't a good fit for broad preventative public health measures like vaccines.

mchusma 5y ago
Or focus on lowering costs. We learned in the pandemic how fundamentally broken the FDA is. There is no reason that things can't be faster that "operation warp speed" all the time. Or re-focus the monetary models around either markets or patient outcomes. Right now, medicine is not a market, it's a strange game. The most money that can be made is finding a treatment that may provide a modest increased benefit over what is live, then sell it to medicare at "name your own price". This incentives high probability wins (which are typically things we already understand well).
- Ericson2314 5y ago
  By this model vaccines are sadly "too effective" on two counts: - They are preventative. Americans are scared that regular people walk into hospitals and debt peons walk out. We are too sickly and scared for preventative medicine, and like our infrastructure which is never maintained to the point of being in "good working order". - They are O(1) dose. The unity economics of once-and-done is bad. Better to sell something which makes a customer for life. It's really depressing.
- azinman2 5y ago
  > There is no reason that things can't be faster that "operation warp speed" all the time. Because money. Operation warp speed started mass manufacturing at the same time as clinical trials. 70% of drugs fail the 3rd stage of trials, so that would be a hugely wasteful endeavor to parallelize this when failure is the norm.

jcims 5y ago

Many cancers exhibit immunosuppressive qualities that allow them to co-exist in a healthy immune system. It seems possible that mRNA-based therapies could be used to interfere with those mechanisms (eg binding to PD-L1, etc). The delivery mechanism for the mRNA appears to be the primary innovation and I wonder if it would be possible to target it at specific cells. In the cancer context if you could differentially target the mRNA delivery to cancerous tissue, the 'payload' could be more generally cytotoxic but only affect tissue proximate to cancer cells. This seems like it's on the order of CRISPR for potential to change the landscape of medicine in the next 50 years.

umanwizard 5y ago
Possibly naive question: if you can differentially target any particular thing to cancer cells specifically, why not just deliver poison to kill the cells directly? I.e. chemotherapy but without any of the nasty side effects.
- jcims 5y ago
  Not naive at all. I didn't word my question well as my interest is broadly if this new technology gives us any more ability to differentiate the delivery, either by selecting for cancer cells or by only 'activating' within cells that are cancerous. In general there are a number of 'targeted' therapies being developed that don't specifically target the cancer cell, but try to make life more difficult for the cancer by broadly impacting a cell's ability to hide, replicate and accumulate...features that the rest of a healthy human tissue is less dependent upon.
- wgolsen 5y ago
  One version of what you are describing is called an antibody-drug conjugate. There are about a dozen ADCs approved and many more in various stages of development
- 8note 5y ago
  I'd prefer to have the poison not have to be in the same process as the detection? The detector likely needs to enter or interact with the cell regardless of whether it's cancerous

dukeofdoom 5y ago

hair loss?

Xenoamorphous 5y ago
I know it’s maybe pure vanity and I definitely wish to see cancer cured first but I think the psychological impact of hair loss, especially in young people (<25), is often underestimated.
- thijsvandien 5y ago
  I think you can easily make that <45 in case of men, and don't forget about women.
- rocgf 5y ago
  For better or worse, it's not the importance of a disease per se that drives innovation, it's money. So assuming that hair loss is the kind of problem that would get people to spend money, then we might see some progress here.
  - lazide 5y ago
    There are many possible ways to quantify importance? And many many stakeholders with often conflicting ideas, demands, and influence. If someone is spending money on something, they are voting that it is important FOR THEM - and more important than whatever else they would have done with the money. If politicians/government aren’t spending money on something - despite saying it’s important - that is a very clear signal that their words and their actions do not align. We have words for that too. If they don’t even bother saying words about it, then that is a clear signal not enough pressure is being applied to make it even a pretend priority no?
- fma 5y ago
  I don't have experience in this field...but w/ hair, someone can get grafts which supposedly look better than plugs from decades ago?

rossmohax 5y ago

Why this article is so Rossi centered? Did he play key role in mRNA breakthrough?

khendron 5y ago
Because the article is about him and the company he (co)founded.
caturopath 5y ago
Because he/his company is the subject of the article? The headline doesn't make that all that clear, but everything about the article seems to.

ppf 5y ago

The next Covid-19 variant?

perardi 5y ago
At the risk of responding to a throw-away comment: https://www.technologyreview.com/2021/01/13/1016098/moderna-variant-coronavirus-vaccine-update/ https://www.technologyreview.com/2021/01/13/1016098/moderna-... They can retool very, very quickly. The slight unknown is running another trial.

coldcode 5y ago

mRNA seems almost like a biological programming language; if you can determine how to build a protein that triggers the body's immune system to attack something you want to destroy it's just a matter of design and testing. I wonder if you could build a real language that you could use to design a sequence and automate the testing.

deleted 5y ago
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arrosenberg 5y ago
You could, but keep in mind mRNA occurs in 3D and thermodynamic and kinetic forces play a huge role in biochemistry, so it’s quite a bit more complicated than your average program.
- inglor_cz 5y ago
  Well, that is why it comes 50 years later than, say, Kernighan and Ritchie standard of C. The know-how and hardware of today are just enough for the 1.0 of mRNA vaccines, so to say. How will the fourth or fifth generation look like, is probably beyond our imagination right now.
bqmjjx0kac 5y ago
Not quite what you're asking for, but check out CRN++ [0], a programming language built on chemical reaction networks (CRN). [0]: https://arxiv.org/abs/1809.07430 https://arxiv.org/abs/1809.07430
dehrmann 5y ago
I still find describing anything in biology as a "programming language" to be a bit generous. It still feels more like fiddling with inputs to an ML model.

ProjectArcturis 5y ago

There are a lot of folks excited about mRNA as a "programming language" for the body. And it kind of is, but it's more complicated than that. The critical thing is that mRNA is extremely immunogenic -- that is, it provokes a strong immune response. Makes sense, since evolutionarily when we had little particles delivering RNA strands to our cells, they we viruses. So, that's great for vaccine production. Not so great for other diseases. Cystic fibrosis, for example, the body fails to make one specific protein. We (probably) can't just program it to produce that protein, because it would also train the immune system to target that protein. The best non-vaccine targets are probably cancer, where you want to get the immune system revved up against a tumor.

im3w1l 5y ago
What about hiv?
- simcop2387 5y ago
  HIV is a virus, so it would seem to be a good candidate for mRNA since you'd want to make it generate an aggressive and early response to the virus. I can't even guess though what challenges would arise given that HIV likes to target the immune system itself.
  - unnouinceput 5y ago
    This might shed some light: https://www.businessinsider.com/new-hiv-vaccine-could-be-moderna-mrna-success-story-2021-4 https://www.businessinsider.com/new-hiv-vaccine-could-be-mod...
CorrectHorseBat 5y ago
I thought they solved that by replacing U by 1-methyl-3'-pseudouridylyl in mRNA vaccines? I can imagine it's not great for vaccines either, you want the immune system attack the spike the mRNA codes for, not destroy the mRNA before it can do it's thing. https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...

ecedeno 5y ago

Moderna has a public development pipeline. It shows they are working on, among other things, an HIV vaccine and vaccines/therapies for multiple types of cancer. https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline

deleted 5y ago
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est31 5y ago
Plus a flu vaccine: > mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [...] > One limitation of the current flu vaccines is that they take about six months to develop, meaning scientists must choose which strains they think will be prevalent in the next flu season — even before the current one is over. So by the time the vaccines are ready for distribution, a different strain may have emerged as the better target. > An mRNA flu vaccine, on the other hand, can be developed in about a month or so, giving researchers much more time to determine which strains to protect against. https://www.washingtonpost.com/health/2021/04/11/mrna-flu-shots/ https://www.washingtonpost.com/health/2021/04/11/mrna-flu-sh... The flu vaccine seems to me to have a better chance of working than an HIV vaccine because we have been trying for decades to come up with one for HIV, without any success at all. I'm not saying that their attempts won't work either, but it's more of a bet than a flu vaccine. An iterative improvement on the existing flu vaccines would still be very helpful.
- lisper 5y ago
  > by the time the vaccines are ready for distribution, a different strain may have emerged as the better target I have never understood this. How many strains are there? I thought there were only like 4 or so. Why don't they just do them all every year?
  - cannaceo 5y ago
    There are subtypes of each. Influenza A and B cause the seasonal flu. The subtypes are named by their hemagglutinin (H) and neuraminidase (N). E.g. H1N1, H5N9, etc.

cigaser 5y ago

Well, it will treat everything. Soon it will be generic technology, accessible to any low-tier lab with "RNA printer". Any country will be able to download medication from internet. And in most places it is impossible to copyright naturally occurring RNA sequence.

subpixel 5y ago

Tick-borne diseases are not all similar but many of them are very, very nasty and Lyme Disease is not the worst of them. I’d love for my kids to be able to play in the weeds and woods with abandon the way I did.

createmyname 5y ago

and rossi thinks this way: "Immortality is not something that that will ever be achievable" well, noted.

lukeschlather 5y ago

Scientifically and medically, vaccines seem extraordinarily exciting as a simple tool that can permanently eliminate problems. Treatments sound very exciting if I were running a business, but scientifically less so. I'm really glad that we've developed these great mRNA vaccines, and I hope that a business drive for recurring revenue doesn't chase people back to merely looking for treatments.

sk1459 5y ago
Permanently? I thought the standard of performance has become “reducing symptoms, maybe, we think, we’re not really sure. This is probably safe though”
- fighterpilot 5y ago
  True for anti-depressants. Evidence is extremely weak and the large majority of the effect in anyone below severe depression is known to be placebo.
dehrmann 5y ago
Once drugs go off-patent, the subscription model is a lot less appealing. Even before then, allowing vaccines to sell for $200 per dose (I'm just making up this number) would encourage vaccine production. But you're right that this is an example of markets not doing the right thing, so it might take government, or even insurance company subsidies on vaccine development.
- rsynnott 5y ago
  That’s not an outlandish number; retail price of the HPV vaccine in developed countries is about 200 euro a dose (though in practice usually paid by health services). They get a lot cheaper once out of patent, of course.

rdlecler1 5y ago

Greenlight Biosciences (one of our portfolio companies) is using RNA as a highly targeted-species-specific pesticide.

DocTomoe 5y ago
This honestly is highly concerning - if that can be done for species, the next step could be to target ethnicity. I feel like this is one of those Oppenheimeresque moments in human history.
- lazide 5y ago
  It’s been tried and done before via chemical and biological methods (if you don’t want to sleep for awhile, check out what has been declassified on THOSE topics and realize that is what they were OK releasing to the public!). The problem of course is that in deploying it, you’ll inevitably kill a bunch of your own - no population is so consistent you won’t kill a bunch of senior leaders who had parents 3 generations ago who were transracial or whatever and lied about it - and it will inevitably turn everyone in the world against you. Even states like NK or Iran need friends, and those friends would have enough casualties from anything like this there is no scenario I can imagine anyone would intentionally release something like that. Doesn’t mean a mad scientist type would cook it up accidentally in the garage, but there are always real world constraints stopping wide spread (physics sometimes, often effectiveness limits or the like).
  - parshua 5y ago
    Why do you bring Iran or NK into this? Let's get it straight: Until now, the only counties who have actually tried genocide on industrial scale, have performed inhumane tests on live subjects of other cultures or used Nukes on civilian targets have been mostly western. Heck, they were literally wiping each other out right until 75 years ago. They are also the ones actively ganging up and invading others TODAY. What delusion suddenly caused you to think it is again 'others' who are trying to wipe you out?
    - 5y ago

hyko 5y ago

Started reading to find the answer, but gave up wading through the hagiography.

2OEH8eoCRo0 5y ago

What can companies do to ease the public's worry about mRNA vaccines? I work with a number of people who will not get an mRNA vaccine until they are better understood.

dehrmann 5y ago
Wait 5 years.
ALittleLight 5y ago
The answer seems straightforward then. More research to better understand mRNA vaccines and their consequences plus an effort to communicate what is found in a way that is digestible for lay people.
- tolbish 5y ago
  How much more easily digestible can you get than this? https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different...
  - ALittleLight 5y ago
    I suppose that gets points for being easily digestible, but it is also from a source that has knowingly lied to the public about covid safety in the past year (masks), it doesn't address any specific concerns related to the vaccine, and this document itself is obviously wrong. For example, it calls the vaccine a "a harmless piece" of mRNA when side-effects to the vaccine that are fairly considered harmful (fever, feeling bad, malaise, etc) are well documented and commonly known. If they wanted to do a good job, the information should come from a trustworthy source, it should present the best arguments against the vaccine, and discuss the merits and lack thereof of those arguments. It should genuinely present the risks and the benefits and a good analysis of the tradeoffs. This document clearly falls well short. You can't expect to convince people like this.

r3pl4y 5y ago

#ExplainLikeImFive Could somebody explain to me what a PVC (Personalized Cancer Vaccine) is? Like what is the personalized part in there? Is there really a realistic scenario in which we'll get some regular vaccination and then we'll be cancer free in the future?

zaphod12 5y ago
Ok, so cancer is essentially a blanket term for describing that you have a group of cells in your body doing uncontrollable runaway mitosis (replicating themselves). But the thing is that it's caused by hundreds of different mutations to your cells in thousands of combinations. So developing a single way to combat all of this is super hard. But if we can identify your particular set of mutations and train your body to attack cells with those, we can get rid of your cancer and prevent it from returning. There are a few strategies for this and it's how some of the most incredible cancer therapies of the last few years work...those are just only applicable to certain very specific mutations.
- r3pl4y 5y ago
  Thank you very much
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throwaway879 5y ago

Do the concerns raised here have any merit? https://osf.io/epr24/ https://osf.io/epr24/

throwaway879 5y ago
Why would anyone down-vote a question asking if there is any merit to some concerns raised by a clinical researcher? The target audience is people working on mRNA vaccines who might be able to shed some light.
- halfjoking 5y ago
  I'm with you. I have no idea why people don't question anything about the capabilities/consequences of this tech.
throwaway879 5y ago
To those downvoting: “The most worrisome part, he said, is that antibodies also can make subsequent infections worse, creating so-called antibody-dependent enhancement. Two vaccines — one against a coronavirus in cats and another against dengue, a flavivirus that affects humans — had to be withdrawn because the antibodies they induced caused potentially fatal reactions. If an antibody binds weakly against these viruses or falls to low levels, it can fail to “neutralize” the virus, but instead help it get into cells.” https://news.berkeley.edu/2020/09/09/for-an-effective-covid-vaccine-look-beyond-antibodies-to-t-cells/?fbclid=IwAR2T98YYuKw1FkK4yYUbwpkQTk7hP_WOO-3tqtPY3W_7d3qiPGejex-hlHM https://news.berkeley.edu/2020/09/09/for-an-effective-covid-...
thewileyone 5y ago
https://www.pnas.org/content/116/39/19727 https://www.pnas.org/content/116/39/19727

lucb1e 5y ago

Because it's buried in some two thousand words: > helping cells produce tissue to heal from events such as cardiac arrest > beyond simple vaccines [...] mRNA therapeutics might be tailored to instruct a person’s immune system to fight their specific type of cancer, or target protein deficiencies in specific organs, and without the toxic side effects of traditional medications. > “My personal moonshot is snake venom, and antivenoms for snake bites,” he says. [...] “You inject it into a person, and within hours the protein that you wish is being expressed,” he explains. The final product of such research, he imagines, would be an antidote that could work for the most lethal species of a specific area, delivered in a way that can be preserved for long times in very remote areas—for instance, a powder that can be stored for long periods of time and reconstituted quickly. This is literally all the info I found that is actually relevant to the interesting headline. The rest of the article is about this person's career and what funding vaccine companies got in 2020.

deleted 5y ago
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cies 5y ago
Thanks for the TLDR. Based on this I'll not read it.
prvc 5y ago
Thank you for the summary. We know we're deep in the weeds when heart disease and cancer are the afterthoughts among candidate diseases to treat.
spurgu 5y ago
I think another key takeaway is that mRNA didn't really seem to interest anyone until the pandemic came along.
- karmelapple 5y ago
  When you say anyone, do you mean anyone with massive funds to finance a big effort with mRNA? Because that would also be wrong. This comment is either just wrong, or at least missing some very important context. There’s a massive amount of research about mRNA. Gene therapy, vaccines, lots more. And there was money already sunk in to have mRNA vaccines at a proof of concept stage before the pandemic. There just never was the urgency to use mRNA in a vaccine until the last 15 months. But mRNA research is all over the place, and not just in vaccines. Source: my life scientist partner Edit: Google search for RNA institute turns up lots of results at universities all over the place: https://www.google.com/search?hl=en&q=institute%20for%20rna%20biology https://www.google.com/search?hl=en&q=institute%20for%20rna%...

lapalmian 5y ago

BioNTech's current development presentation: https://investors.biontech.de/static-files/53947c63-dd5c-44d3-8543-87c1ecad96a1 https://investors.biontech.de/static-files/53947c63-dd5c-44d... CureVac's pipeline can be found here on page 6: https://www.curevac.com/wp-content/uploads/2021/04/20210421-CureVac-Investor-Handout.pdf https://www.curevac.com/wp-content/uploads/2021/04/20210421-...

Sommer 5y ago

Could there be mRNA applicability to food allergy treatments, peanut allergies in particular?

senbarryobama 5y ago

Can they help Parkinson’s?

throwaway879 5y ago

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827936/pdf/vaccines-09-00036.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827936/pdf/vac...

alcuadrado 5y ago

> Derrick Rossi doesn’t quite see it this way, but he kind of saved the world. > > In 2008, he began researching messenger RNA (mRNA), building on the long-ignored work of Hungarian researcher Katalin Karikó What?! Katalin Karikó is an SVP at BioNTech, the lab that created Pfizer's vaccine.

jonstewart 5y ago
Yes, and... she was long ignored before that. https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/ https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-... https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-kariko.html https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-k...

tonymet 5y ago

Anyone know the answer to why the treatment failed after 20 years of research and suddenly succeeded ?

da02 5y ago

Isn't it too early to think about mRNA therapies? VAERS data released today showed 118,902 reports of adverse events following COVID vaccines, including 3,544 deaths and 12,619 serious injuries between Dec. 14, 2020 and April 23, 2021: https://childrenshealthdefense.org/defender/vaers-significant-jump-reported-injuries-deaths-after-covid-vaccine/ https://childrenshealthdefense.org/defender/vaers-significan... The Orange County Coroner's office is investigating the death of a woman who died just days after she received her second dose of the Moderna vaccine: https://abc7.com/health/oc-womans-death-after-vaccination-spurs-concern-from-family/10562182/ https://abc7.com/health/oc-womans-death-after-vaccination-sp... Meanwhile: Using a protocol of zinc, hydroxychloroquine or ivermectin and one antibiotic in combination with inhaled budesonide and/or intramuscular dexamethasone... The early ambulatory treatment regimen was associated with estimated 87.6% reduction in hospitalization and 74.9% reduction in death (p<0.0001): https://trialsitenews.com/texas-physician-researchers-case-series-finds-reduction-in-covid-19-hospitalization-by-87-6-death-74-9/ https://trialsitenews.com/texas-physician-researchers-case-s...

stbtrax 5y ago
How would an antibiotic help with a viral infection? Might as well start using some essential oils and homeopathy. If that regimen actually worked, we'd probably see it more widely used and studied. They investigate each death reported to VAERS to see if it was actually vaccine related. Given how many millions of doses were given out, and especially to people that were already old or clinging on to life, 3,544 is not unexpected. None of those were directly attributable to the vaccine.
- da02 5y ago
  Maybe the antibiotic is for Tuberculosis? https://www.cdc.gov/globalhealth/stories/2020/tb-covid.html https://www.cdc.gov/globalhealth/stories/2020/tb-covid.html
soared 5y ago
Please don’t play armchair medical researcher. The question you’ve asked is much larger 3 urls, one of which is an investigation into a single event among hundreds of millions of doses. Your third link is not remotely relevant. The article is not discussing covid treatments, but rather the category of vaccine. Zinc isn’t going to cure cancer.

collyw 5y ago

Maybe worth checking the long term effects before forcing these vaccines on other things. https://pubmed.ncbi.nlm.nih.gov/33300001/ https://pubmed.ncbi.nlm.nih.gov/33300001/

Jemm 5y ago

The article totally glosses over Katalin Karikó who really should be getting the credit.

pajko 5y ago

What are the technology's limits? Would it be possible to create mRNA shots to grow more muscle tissue, regrow teeth or lost limbs?

monopoledance 5y ago

Could mRNA injection temporary restore activity for loss-of-function mutations like p53 deletion in cancer? The general, inherent hurdle in cancer treatment is discriminating individualist, misbehaving cells from cooperative, healthy ones. From what I got, p53 isn't not expressed in healthy cells, but rather inactivated. Therefore it may be possible to systemically restore it in all cells, without inducing apoptosis in well-behaving cells. This would be exciting, because it would enable cancer treatment avoiding selection based on cell signature, or "finding a target". Effectively restoring functionality of cell cycle guardians, which will then suicide the cancer cells seems like an attack vector very hard to evade for cancer cells. You wouldn't ask "who is misbehaving?", but rather shortly reign "everybody does as I say, now!". Cancer cells can get rid of all the surface proteins (targeted by immunotherapy) and even gain root acce.. omnipotent stem cell characteristics (game over), they cannot shake the programmatic hallmarks of cancer, without stop being cancer. And the most important feature isn't rabid metabolism (targeted by chemo), but unchecked cell division. Chemo doesn't work well on indolent/non-aggressive cancers, as their metabolic signature is not discriminating. But who cares, if cells lost e.g. the p53 altogether, if we can force the machinery onto them regardless? No need to diff/patch the source, bring the bytecode to the compiler and fix the system until broken for good. All we want is them to "wake up" briefly and take responsibility for the mess they got at hand. (Of course, it wouldn't be possible to flood the body with "activated p53", as that would probably suicide all cells (although it makes for a pretty scifi murder-agent), and the activation itself may offer an escape... until people figure out the whole shop.) * https://en.wikipedia.org/wiki/P53 https://en.wikipedia.org/wiki/P53 * https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer

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