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What can mRNA treat next?

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Re: What can mRNA treat next?

#141

Post by roywiggins »

agumonkey wrote: post #109
ecedeno wrote: post #53

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

brings an odd question, will we have to have artifical exposure to diseases just to ensure our immune system is capable ?

One theory about the 1918 flu us that it hit young people harder because older people had encountered a similar flu already, before the younger generation were born.

But in general, being exposed to (say) seasonal flu every year might not help you at all when a new strain of pandemic flu shows up. The 1918 flu tore through young healthy people.

Re: What can mRNA treat next?

#142

Post by xKingfisher »

fma wrote: post #105
Xenoamorphous wrote: post #24

Earlier quoted context omitted.

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.

I don't have experience in this field...but w/ hair, someone can get grafts which supposedly look better than plugs from decades ago?

They still have a number of issues.

* They're expensive (~4-8 dollars per follicle) with a single transplant being 1000-5000 follicles. Severely bald men may need multiple

* There is a finite number of follicles that can be transplanted.

* Permanent scarring in the donor zone.

The ultimate treatment would be either hair cloning (still a ways out, very expensive) or a way to reactivate the dormant follicles. Presumably if you could solve the latter you would become very rich very quickly.

Re: What can mRNA treat next?

#143

Post by robbiep »

vmception wrote: post #125
est31 wrote: post #64

Earlier quoted context omitted.

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 ar…

It seems like with HIV they can simply sequence the prevalent evolutionary outcome in your body within a month and give your body the blueprint to destroy that version What typically happens with HIV is that the body kills most of it initially, but the remaining ones keep rapidly evolving until an iteration evades your immune response, this takes about 12 years. Seems like an mRNA vaccine could be done every 3 years…

That's not quite true - HIV of course mutates but in-patient mutations are generally considered to have a negligible effect on outcomes/have a negligible effect as a driver of morbidity .

What is the big driver of HIV is in the name, it's a Immunodeficiency virus - it kills CD4+ T cells and other cells of the immune system. At a certain point you don't have enough CD4+ T cells left and you lose your adaptive/cell-mediated immune system and then you're in big trouble. Essentially it's a war of attrition and unless you're part of some tiny proportion of people who have either a form of immunity against it or an immune system that for whatever reason is able to continue waging war on it then you will succumb

Re: What can mRNA treat next?

#144

Post by drzaiusapelord »

da_big_ghey wrote: post #102
toast0 wrote: post #88

Earlier quoted context omitted.

Now that mRNA is productionized (or at least on the path towards it), and has been used in hundreds of millions of people without apparent major negative short term effects, the barrier is lower for other targets which no longer have to prove the whole technology is safe, effective, and producable. We have two examples of safe (so far), effective and mass produced mrna vaccines; so it's probably easier to get funding…

how much money in cure HIV? largest endemic area is probably subsaharan Africa, not much in money there. In western nation it mostly is disease for gays or ocasional unlucky blood transfusion receive person [0]. i am not say that cure for it is bad - it is in obvious good - why did Moderna make choice for to research this cure in specific over other? https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/cdc-msm...

This is hate speech.

Re: What can mRNA treat next?

#145

Post by [deleted] »

lucb1e wrote: post #134

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,…

[deleted]

Re: What can mRNA treat next?

#146

Post by cies »

lucb1e wrote: post #134

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,…

Thanks for the TLDR. Based on this I'll not read it.

Re: What can mRNA treat next?

#147

Post by lazide »

parshua wrote: post #131
lazide wrote: post #100

Earlier quoted context omitted.

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…

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 d…

Huh? I guess that depends on your definition of western I guess, since Japan certainly had no issues genociding, testing chemical and biological weapons, and all that other stuff on a wide swath of Eastern Asia? Russia isn’t generally considered by anyone I’ve run across as a ‘Western’ country either, and they had (still may have) a massive program.

Near as I can tell, every industrialized power has gone through the phase.

The comment about nukes is weird, since I believe the US is the only power to ever nuke someone in anger - and near as I can tell, plausibly used it as little as possible and in self defense (though we could talk ourselves blue in the face on that point).

Nothing would have stopped the US from carpet nuking Japan for instance at the time, except some minor logistical hiccups.

My comment about Iran and NK is specifically because they’re consistently isolated by (and start fights/ideologically align themselves opposite) the bulk of countries.

They’ve been, and continue to encourage being ‘others’. I pointed out, they still have no incentive to wipe any groups out/start targeted plagues, wouldn’t start something like this, so why would anyone else?

Re: What can mRNA treat next?

#148

Post by tum92 »

JPLeRouzic wrote: post #65
ProjectArcturis wrote: post #35

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…

> We (probably) can't just program it to produce that protein, because it would also train the immune system to target that protein. I am not a scientist but my understanding is that the immune system targets only what it is trained against. It doesn't target anything which is non-self without being trained beforehand. IMO if it was otherwise there would be no need for vaccine. So I think that it is quite feasible to…

Immunology is wildly complicated so my description is going to fall short of reality, but my understanding of the role of the adaptive immune system as it would relate to mRNA therapies is different.

Lymphocytes, or T cells & B cells, are immune cells which have receptors on their surface that recognize a specific, tiny chunk of protein. For any given lymphocyte, the type of receptor on its surface is fixed for its life and that receptor is able to recognize exactly one distinct protein chunk.

Through some very cool mechanisms, very early on in life we all develop a massive number of lymphocytes, each of which recognize different protein chunks. I've not read any research which quantifies the scope here, but it's not unreasonable for the sake of a thought exercise to the assume that at one point we all have a lymphocyte receptor repertoire that's capable of recognizing every conceivable natural protein. Through what I consider one of my top 10 most jaw-dropping biological mechanisms [0], we cull the population of lymphocytes that recognize self, leaving us with a cell population capable of recognizing and responding to every non-self protein conceivable. No training is needed here, each of us at this exact moment has several T cell and B cell populations ready to recognize proteins produced by the next novel pandemic causing virus, whatever future protein mRNA vaccines might make, and whatever proteins these future mRNA therapies might produce.

What you refer to as training is probably more like immunological memory, which allows for a ramping up of the immune response on a quicker timeline. We give vaccines where it's generally not safe (or survivable) to wait out an effective immune response, because the disease causes so much havoc in the meantime. This doesn't really apply for the introduction of novel, useful proteins.

Your point about Onasemnogene abeparvovec is a very interesting one. I'm truly only guessing here, but people with SMA almost universally produce functional protein via SMN2, but very little of it. It's not enough to serve its function, but is perhaps enough for effective self-tolerance. I'm also not entirely sure about the timeline of self-tolerance development, it's possible Onasemnogene abeparvovec is given young enough to allow effective tolerance development!

[0] - https://en.wikipedia.org/wiki/Autoimmune_regulator

Re: What can mRNA treat next?

#150

Post by manwe150 »

coderaptor wrote: post #120
agumonkey wrote: post #109

Earlier quoted context omitted.

brings an odd question, will we have to have artifical exposure to diseases just to ensure our immune system is capable ?

I'd also like to know where I can read further on discussions on this. My understanding is that it's the same for chickenpox - that lack of frequent natural exposure now requires artificial exposure with boosters to prevent shingles. Feels like vendor lock-in to me - often valuable but with some downsides that need to be evaluated on a case by case basis.

From my layman's reading (start from https://en.m.wikipedia.org/wiki/Shingles#Epidemiology), I think the chickenpox vaccine is potentially somewhat the inverse of vendor lock-in: that giving the vaccine to children decreases the possibility of shingles complications later for them, while studies potentially show an increase in the prevalence of complications among unvaccinated older folks, thus making it relatively worse to not vaccinate for it, as you get older, and as others opt into it. Since there's also multiple shingles vaccines now, this sounds to me more like a typical network effect from vaccination?

To make up an unrelated tech example of that, my impression was this would be like picking a Blackberry phone, while all your friends have Windows phones. You weren't forced to pick a Blackberry by vendor lock-in, but you may miss out on being in some social circles. Changing that group dynamic would require everyone to switch, not just on a case-by-case basis. But in this example though, the Window's phones (aka vaccination) have strictly more features than the Blackberry (aka kills you less often), so if you can afford to (aka you have an average immune system), it would be more logical to get a new phone yourself and join the network, than to ask all of your friends to get new phones.

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