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What can mRNA treat next?

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Re: What can mRNA treat next?

#91

Post by elcritch »

lisper wrote: post #73
cannaceo wrote: post #71

Earlier quoted context omitted.

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.

OK, but that doesn't really answer my question. Turns out the answer can be found here: https://www.cdc.gov/flu/about/viruses/types.htm "There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease (known as the flu season) almost every winter in the United States. Influenza A viruses are the only influenza viruses known to cause flu pandemics, i.e., gl…

It seems they could pre-make vaccines for all 131 extant types and then mix the flu shots based on the current season. Though, likely that wouldn’t be economical.

It does raise the question of why they couldn’t just put a bit of all 131 subtypes in the vaccine. Or if that’d overload the immune system, say, the X subtypes most likely to makeup say 99% of probable flu season strains.

Re: What can mRNA treat next?

#93

Post by elcritch »

hirenj wrote: post #31
jcims wrote: post #9

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 ta…

I was thinking about this very subject this morning, and I realised the mRNA stuff actually isn’t the exciting part. It’s the packaging in lipid particles that is much more interesting. We can get away with this approach for vaccines because we (largely) don’t care where we deliver the payload to, just as long as we get mRNA to a cell where it can make the protein. Not sure about current formulation, but I read most…

An alternative approach would be to learn enough to make mRNA “programs” that once inside a cell could determine cancerous vs healthy cells. There’s been research on computations using DNA, and many natural pathways do similar “calculations”, that it seems feasible to create a “if specific xyz protein/carbohydrate/etc in cell exceeds threshold trigger cell death pathways”. Then injection in a tumor mass should be sufficient. The mRNA program might only need to be partially accurate to be more effective than many chemotherapy’s.

Re: What can mRNA treat next?

#94

Post by dhosek »

inglor_cz wrote: post #85
DanielBMarkham wrote: post #28

Earlier quoted context omitted.

I agree. It's easy to overstate things, but over the next several decades I could easily see a computational personalized approach to fighting cancer: read the unique immunosuppressive markers, sort out what's tractable and what's not, then deliver a mRNA payload for that particular cancer for that particular person. For the incredibly small amount that I know, it looks like a game changer. (Like everything else, tho…

I think this is precisely what BioNTech has been doing with melanoma. Not in a few decades, they already had living patients with personalized vaccination against their own melanomas in 2019: https://www.nature.com/articles/d41586-019-03072-8 If this immunotherapy gets developed further, the next generations of humanity may look at cancer in the same way that we look upon bacterial diseases: unpleasant, the threat of…

Although given how we've squandered (and continue to squander) antibiotics, future generations may view bacterial diseases the way past generations did.

Re: What can mRNA treat next?

#95

Post by CodesInChaos »

inglor_cz wrote: post #85
DanielBMarkham wrote: post #28

Earlier quoted context omitted.

I agree. It's easy to overstate things, but over the next several decades I could easily see a computational personalized approach to fighting cancer: read the unique immunosuppressive markers, sort out what's tractable and what's not, then deliver a mRNA payload for that particular cancer for that particular person. For the incredibly small amount that I know, it looks like a game changer. (Like everything else, tho…

I think this is precisely what BioNTech has been doing with melanoma. Not in a few decades, they already had living patients with personalized vaccination against their own melanomas in 2019: https://www.nature.com/articles/d41586-019-03072-8 If this immunotherapy gets developed further, the next generations of humanity may look at cancer in the same way that we look upon bacterial diseases: unpleasant, the threat of…

> in the same way that we look upon bacterial diseases: unpleasant, the threat of treatment resistance is there

Those treatment resistances are quite different. Resistant bacteria spread to other people, while cancer is almost always limited to a single patient. So it the treatment works for a certain fraction of cancers, it'll stay at that level, unlike bacteria which become increasingly resistant over time.

(I guess that in the very long term that might not be true, since natural cancer resistance will offer less of an evolutionary advantage. But that assumes that humanity will remain in a similar state as currently, which seems unlikely.)

Re: What can mRNA treat next?

#96

Post by inglor_cz »

CodesInChaos wrote: post #95
inglor_cz wrote: post #85

Earlier quoted context omitted.

I think this is precisely what BioNTech has been doing with melanoma. Not in a few decades, they already had living patients with personalized vaccination against their own melanomas in 2019: https://www.nature.com/articles/d41586-019-03072-8 If this immunotherapy gets developed further, the next generations of humanity may look at cancer in the same way that we look upon bacterial diseases: unpleasant, the threat of…

> in the same way that we look upon bacterial diseases: unpleasant, the threat of treatment resistance is there Those treatment resistances are quite different. Resistant bacteria spread to other people, while cancer is almost always limited to a single patient. So it the treatment works for a certain fraction of cancers, it'll stay at that level, unlike bacteria which become increasingly resistant over time. (I gues…

I know, it is an imperfect analogy. But thank you for noticing and explaining my shortcut to other readers.

Cancers are very patient-specific, and the main threat with immunotherapy is that the targeted cancer adapts quickly enough to escape the immune system again.

Re: What can mRNA treat next?

#97

Post by lazide »

elcritch wrote: post #91
lisper wrote: post #73

Earlier quoted context omitted.

OK, but that doesn't really answer my question. Turns out the answer can be found here: https://www.cdc.gov/flu/about/viruses/types.htm "There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease (known as the flu season) almost every winter in the United States. Influenza A viruses are the only influenza viruses known to cause flu pandemics, i.e., gl…

It seems they could pre-make vaccines for all 131 extant types and then mix the flu shots based on the current season. Though, likely that wouldn’t be economical. It does raise the question of why they couldn’t just put a bit of all 131 subtypes in the vaccine. Or if that’d overload the immune system, say, the X subtypes most likely to makeup say 99% of probable flu season strains.

They could - but up until recently no one cared enough, both for R&D spend and to get or mandate enough shots for it to work at it’s stated goals.

We’ve had people even recently refusing to give their kids polio, tetanus, or measles vaccines - and even 5 minutes of honest research or questions to a doctor will make quite clear how bad an idea THAT is. Getting 100+ flu vaccines, all which would have to go through a pipeline taking nearly a decade, when ‘nothing bad has happened’ on that topic for a hundred years?

Ain’t nobody going to pay for that.

We’ll see how the calculus is different soon. I for one would rather my tax dollars go towards figuring something like never having the flu again than blowing up some random middle eastern country a couple more times.

Re: What can mRNA treat next?

#98

Post by raverbashing »

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…

> mRNA as a "programming language" for the body

Kinda. Programming but more like a browser JS.

You're not changing anything (your DNA) and whatever you're making is temporary and limited (especially because you can't have anything too complex or long as mRNA without that breaking up).

Re: What can mRNA treat next?

#100

Post by lazide »

DocTomoe wrote: post #90
rdlecler1 wrote: post #70

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

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.

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).

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