[deleted]
What mRNA is good for, and what it maybe isn’t
41–50 of 152 posts
Re: What mRNA is good for, and what it maybe isn’t
#42I 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…
I think you meant 30 µg (micrograms). And it is indeed tiny. Even for LSD "the only drug measured in micrograms", a typical dose is around 100µg. Most drugs (both the legal and illegal kind) are in the tens of milligram range.
> LSD "the only drug measured in micrograms"
Carfentanil is probably more potent then LSD, here is a lethal dose:
https://mediad.publicbroadcasting.net/p/wosu2/files/styles/x...
"For pain relief, a unit of carfentanil is one hundred times as potent as the fentanyl, five thousand times as potent as heroin, and ten thousand times as potent as morphine, despite having only 14 to 135 times the affinity for the mu receptor."
Re: What mRNA is good for, and what it maybe isn’t
#43“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?
Before hundreds of millions of people were vaccinated, the agreed on success was from the initial clinical trials, which saw virtually no infections in the vaccinated group, and hundreds in the unvaccinated. Now, with so many people vaccinated, more than 90% of new cases are in people who are unvaccinated (and virtually no COVID-related deaths).
Re: What mRNA is good for, and what it maybe isn’t
#44Earlier 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.)
What has the FDA done to start gathering this data?
Re: What mRNA is good for, and what it maybe isn’t
#45I 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…
[deleted]
Re: What mRNA is good for, and what it maybe isn’t
#46Earlier quoted context omitted.
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.
Thanks, this is quite re-assuring since I am worried about prions as well. Could you please suggest a link for me to further educate myself on how unlikely this is ?
This isn't bad: https://www.scientificamerican.com/article/what-is-a-prion-s...
The basic punchline is that while prion diseases are terrifying, there's not a lot of them and they are quite specific - you have to have a protein which is already able to adopt that conformational structure, and it has to be a protein we already make natively, as prions only work with what's there.
We are probably still missing part of the picture as well: i.e. the prion diseases which cause problems are brain diseases, we don't see the same issue with other tissues.
It would be difficult to actually induce a prion disease in someone via genetic vaccine in the first place, since prion's notably don't have a genetic component - and in the case of vCJD the infectious and benign protein sequences are the same (i.e. the coding is already something we carry, they're conformational jumps).
Re: What mRNA is good for, and what it maybe isn’t
#47> 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…
It's not clear that mRNA holds any actual advantage for that low-hanging-fruit relative to other approaches though (e.g. protein subunit or DNA-based vaccines).
Re: What mRNA is good for, and what it maybe isn’t
#48Earlier quoted context omitted.
What happens to the unactivated mRNA in that case? I was under the impression that it was typically the actual use of the mRNA by the ribosomes that broke them down generally, but I could be off base there.
The same mRNA can be used by multiple ribosomes. More info and "photos": https://biology.stackexchange.com/questions/54752/can-mrna-b...
Sure, it isn't destroyed immediately and the mRNA is used multiple time, but that's still ultimately the ribosomes damaging the mRNA from use. My question is around how they break down if there aren't ribosomes involved (ie. if the capsules above aren't opened because they weren't exposed to the light trigger).
Re: What mRNA is good for, and what it maybe isn’t
#49[flagged]
Re: What mRNA is good for, and what it maybe isn’t
#50Earlier quoted context omitted.
I think you meant 30 µg (micrograms). And it is indeed tiny. Even for LSD "the only drug measured in micrograms", a typical dose is around 100µg. Most drugs (both the legal and illegal kind) are in the tens of milligram range.
> LSD "the only drug measured in micrograms" Carfentanil is probably more potent then LSD, here is a lethal dose: https://mediad.publicbroadcasting.net/p/wosu2/files/styles/x... "For pain relief, a unit of carfentanil is one hundred times as potent as the fentanyl, five thousand times as potent as heroin, and ten thousand times as potent as morphine, despite having only 14 to 135 times the affinity for the mu recepto…
That carfentanil looks like about a milligram, but impossible to say without knowing its density.