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What can mRNA treat next?

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Re: What can mRNA treat next?

#171

Post by wgolsen »

School-Cotton wrote: post #33
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.

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

Re: What can mRNA treat next?

#173

Post by jbjbjbjb »

lazide wrote: post #118
jbjbjbjb wrote: post #114

Earlier quoted context omitted.

There’s got to be a large market for that given the entire elderly population is offered a flu shot every year. Doing that as a one off would be a huge cost saving.

Not sure it would pay for itself even in 100 years if you use that metric. $20 (likely current retail cost of a flu shot) x the 46 million older adults in the US is a hair less than a billion a year. Making 131 or so effective flu vaccines and getting them through the process with the prior known and effective process? (including all the failed attempts) Hopefully we’d get some economies of scale, estimates [ https:/…

I believe they’d make one shot that would handle 131 flus.

Re: What can mRNA treat next?

#175

Post by agumonkey »

staticassertion wrote: post #121
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 ?

You mean a vaccine?

I meant that in a future where you never have to fight viruses your immune system will be weakened.

Re: What can mRNA treat next?

#177

Post by da_big_ghey »

tecleandor wrote: post #138
da_big_ghey wrote: post #102

Earlier quoted context omitted.

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...

That's an answer right from the 80s and it's completely wrong and against the same statistics you link. In the US heterosexuals account for more than 25% of AIDS infections, not accounting bisexuals and undetermined infections.

i think it are support since 75% still gay and gays is very small section of population. this vast disproportination mean it mostly is still "gay disease". i counter your unacounted factors by my say that maybe some in "straight" population with disease are not wanting to disclose gay. i am wonder if maybe bi sexual are worst because they "leak" disease back into straight population. they are like persons travel between two "bubble" in coronavirus pandemic.

Re: What can mRNA treat next?

#178

Post by da_big_ghey »

dinkleberg wrote: post #139
da_big_ghey wrote: post #102

Earlier quoted context omitted.

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...

Do you ever read what you write before posting it and do a basic morality review? I’m sure there are many valid points to debate which diseases to go after next, but you only consider the money. I’m a capitalist and love making money, but come on! Questioning the choice to go after HIV because the primary people benefiting are too poor or gay? That is insanity.

you are misinterpret of this. i am not say that such would be good, but it are true that company tend for to do this, to mostly go fore money. so why moderna is go after hiv?

Re: What can mRNA treat next?

#179

Post by monopoledance »

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/The_Hallmarks_of_Cancer

Re: What can mRNA treat next?

#180

Post by monopoledance »

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…

I think this is not just because of viruses, but also healthy autoimmunity. Finding even your own cell internals in the bloodstream would mean there is work to do for the immune system. E.g. auto-antibodies may increase with tumor burden, as cell rupture caused by apoptosis, or necrosis attract immune cells and cascade recruitment of more, which is usually a good thing.

Anyway, AFAIK the mRNA breakthrough wasn't with the mRNA itself, but rather the delivery vehicle to avoid said immune response. I don't think your example of cystic fibrosis, and generally chronic illnesses, are prime targets for mRNA based therapy, as the genetic defect isn't causally targeted by mRNA tech. You would force all cells (with non-discriminatory vehicles) to produce the missing protein repeatedly. Much better target for gene therapy.

I don't think people see the future of mRNA in substituting into the delicate machinery of the cell continuously. I think the possible therapy target are of the type raw, simple one-hit wonders. Very much alike traditional medication approaches, with the twist of excellent drug delivery avoiding extracellular pharmacokinetics, e.g. vitamin C has very different, even antagonistic roles in the intra- vs extracellular space, and of course liver-fistpass and immunological clearance. mRNA tech is not gene therapy (although, there is of course effective overlap).

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