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What mRNA is good for, and what it maybe isn’t

blogs.sciencemag.org

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Re: What mRNA is good for, and what it maybe isn’t

#21

Post by H8crilA »

zabzonk wrote: post #20
klevertree wrote: post #5

I wrote a long essay about the same topic and came to similar conclusions as Derek Lowe: https://trevorklee.com/are-mrna-therapies-the-future-of-phar... One thing that I'd like to emphasize is how unbelievably tiny mRNA therapeutics have to be. It's probably around 30 mg, and it's hard to do it more than once every few weeks, at least judging by siRNA therapeutics (which have similar immune issues). 30 mg is really t…

> 30 mg is really tiny Not really. For example the amount of beta blocker I take for my heart problems is 5mg per day - the pill size goes down to 2.5mg.

Not to mention LSD, which is a well below 1mg thing.

Also not sure why it matters at all, if it's under 1g you can administer it pretty much any way you need to.

Re: What mRNA is good for, and what it maybe isn’t

#22

Post by TeMPOraL »

pjscott wrote: post #10
lazyjones wrote: post #7

I am worried about the low level of intact mRNA in those vaccines, esp. as an IT guy. https://www.medicalnewstoday.com/articles/early-concerns-rai... 25-45% randomly modified or defective mRNA doesn't sound safe. It's a bit like machine code with random errors, isn't it?

RNA uses an error-correcting code, and if that fails all that should happen is that some of the proteins your ribosomes create will be misshapen. Your body is good at dealing with foreign proteins.

Except when it isn't. I'm sure this problem has been explored and ruled out, but as a general note, when I read that "all that should happen is some proteins will be misshapen", my mind immediately screams prions.

Re: What mRNA is good for, and what it maybe isn’t

#24

Post by H8crilA »

wbl wrote: post #15
InTheArena wrote: post #2

Derek Lowe's articles during covid have been a huge help trying to navigate the coronavirus hellscape we have been in. It's great to see him start to talk post-covid applications of medicine as things maybe wind down a bit. Delta+ willing

We could retarget the mRNA batches tonight if it wasn't for the FDA not taking this seriously.

Uhm, it is serious if you know anything about drug development history. It always is.

The current mRNA Covid vaccines have a pretty high incidence rate of ongoing rapid swelling and rashes (in the 1/100 to 1/1000 range), and it's still unclear what will happen to the hundreds of thousands of affected people.

Source: https://en.m.wikipedia.org/wiki/Pfizer%E2%80%93BioNTech_COVI...

Also to be found in the adverse reactions database (VAERS) by the CDC.

Re: What mRNA is good for, and what it maybe isn’t

#25

Post by twaway »

My newborn was diagnosed with Sturge–Weber syndrome and mRNA sounds like a potential solution.

The issue is it's rare and united States government approval is expensive and slow. Not something that works well with a degenerative disease.

I'm a bit insane right now admittedly, but given my background and wealth, I'm considering DIY. The technology is there, government is the hold up. Would you let your kid have seizures and cognitive problems because of red tape?

Re: What mRNA is good for, and what it maybe isn’t

#26

Post by gus_massa »

wbl wrote: post #15
InTheArena wrote: post #2

Derek Lowe's articles during covid have been a huge help trying to navigate the coronavirus hellscape we have been in. It's great to see him start to talk post-covid applications of medicine as things maybe wind down a bit. Delta+ willing

We could retarget the mRNA batches tonight if it wasn't for the FDA not taking this seriously.

Retargeting is one of those things that everyone is 99% sure it's safe. But 99% sure in millions of people means thousand of problems and perhaps deaths. So before signing any authorization it's better to wait until the clinical trials are done instead of using gut feelings. (Waiting too much is also bad, so it's a tradeoff.)

Re: What mRNA is good for, and what it maybe isn’t

#27

Post by dragonwriter »

gus_massa wrote: post #26
wbl wrote: post #15

Earlier quoted context omitted.

We could retarget the mRNA batches tonight if it wasn't for the FDA not taking this seriously.

Retargeting is one of those things that everyone is 99% sure it's safe. But 99% sure in millions of people means thousand of problems and perhaps deaths. So before signing any authorization it's better to wait until the clinical trials are done instead of using gut feelings. (Waiting too much is also bad, so it's a tradeoff.)

> Retargeting is one of those things that everyone is 99% sure it's safe. But 99% sure in millions of people means thousand of problems and perhaps deaths.

You seem to be assuming “99% sure it is safe” means “sure that its 99(.9)% safe”. They are...not equivalent.

Re: What mRNA is good for, and what it maybe isn’t

#28

Post by didibus »

> So mRNA-based techniques have a lot of power and a lot of promise. But there’s definitely a low-hanging-fruit area here, and that’s infectious disease vaccines. Beyond that the promise holds up, big-time, but the difficulties mount up as well. It’s going to be a long story with a lot of plot twists, but I’m glad we’re telling it.

Just want to emphasize the conclusion, because if you stop reading before the end, you might think that the article is dismissive of mRNA, its not, just realistic in the remaining challenges for some of the more ambitious outcomes of it.

Re: What mRNA is good for, and what it maybe isn’t

#29

Post by maxerickson »

DaniloDias wrote: post #18

“The huge success of the mRNA vaccination platform” Does anyone know what the agreed upon criteria for asserting the success of mRNA vaccinations is? Aren’t we anticipating an uptick in cases in the US as we approach winter? Why are we assuming success already?

I'm not sure what you mean by "agreed upon", but they are, blatantly, obviously, preventing (lots of) infections in lots of countries at this point.

Re: What mRNA is good for, and what it maybe isn’t

#30

Post by XorNot »

TeMPOraL wrote: post #22
pjscott wrote: post #10

Earlier quoted context omitted.

RNA uses an error-correcting code, and if that fails all that should happen is that some of the proteins your ribosomes create will be misshapen. Your body is good at dealing with foreign proteins.

Except when it isn't. I'm sure this problem has been explored and ruled out, but as a general note, when I read that "all that should happen is some proteins will be misshapen", my mind immediately screams prions .

Prions need to be beta-sheet proteins with specific conformations. They're hard to generate, and certainly are not single-base substitutions - otherwise the biosphere would be riddled with them.
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