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What can mRNA treat next?

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Re: What can mRNA treat next?

#31

Post by hirenj »

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 LNPs end up in the liver from circulation.

The next level of tech is targeting the particles, and then it gets as tricky as other contemporary techs, because you want your targeting mechanism on the prticles to be something resembling a receptor ligand (protein/carbohydrate).

Manufacturing of those (and putting them on a lipid particle) is still a slog. If we figure out nice ways to do that (without reasonable purity) then it doesn’t matter what is in the LNP (e.g put gold particles inside cancer targeting particles and zap your cancer cells dead).

Re: What can mRNA treat next?

#33

Post by School-Cotton »

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…

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.

Re: What can mRNA treat next?

#34

Post by mchusma »

Steuard wrote: post #7

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 straight…

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).

Re: What can mRNA treat next?

#35

Post by ProjectArcturis »

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.

Re: What can mRNA treat next?

#36

Post by vallard »

jcims wrote: post #5
GEBBL wrote: post #2

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.

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.

I really really hope so.

Re: What can mRNA treat next?

#37

Post by Ericson2314 »

mchusma wrote: post #34
Steuard wrote: post #7

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 straight…

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 wh…

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.

Re: What can mRNA treat next?

#38

Post by [deleted] »

coldcode wrote: post #30

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]

Re: What can mRNA treat next?

#39

Post by im3w1l »

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…

What about hiv?

Re: What can mRNA treat next?

#40

Post by altcognito »

Steuard wrote: post #7

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 straight…

I believe the correct packaging mechanism was only conceived in 2018.
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