“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?
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While it could be presented better, I think this point is fair. We seem to mostly be happy to write-off the downsides because 'but the alternative is worse.'
Sure, but let's not stop applying a critical eye and measured caution with things that are still in trial phase with inconclusive evidence for long term success.
RNA and DNA essentially use the same genetic code, which is degenerate and thus somewhat error correcting.
You mean the degeneracy in the last base of codons that I mention? I wouldn't even call that an error correcting: would you count a file type that just skipped every third byte 'error correction'? I wouldn't. This isn't a robust system and most changes to any bases will change the protein sequence. Contrast that to DNA which does have error correction, since there are two strands instead of one and also two chromosom…
I completely agree. I was addressing a confusion of the previous poster.
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…
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.
Read through some of the links in the linked article it must be micrograms.
the theraputics part is different than the immune system response part. they said in the theraputics part you don't get to use the immune system memory because the immune system memory is there to make a foreign enough protein that looks like the virus receptors so the body learns how to kill those proteins. a therapeutic doesn't want you to kill the proteins it creates because the proteins created need to be able to…
Thanks. If I'm correct then the mRNA vaccine introduces proteins that reflect the virus and trigger the immune response? I think I was reading the article as mostly focused on vaccines, but it was focused on cancer treatment, hence my confusion...
The article is talking about multiple possible uses for mRNA drugs, including prophylaxis and non-prophylaxis vaccines (you would not take a vaccine for a cancer before you get it, unless it is to prevent an infection that could cause cancer (HepB, HPV, etc)), and mRNA therapeutics, including ones from protein replacement. For protein replacement, you would have to take the mRNA often, because mRNA degrades. Your immune system has memory, but you won't keep making random proteins after the mRNA goes away.
the theraputics part is different than the immune system response part. they said in the theraputics part you don't get to use the immune system memory because the immune system memory is there to make a foreign enough protein that looks like the virus receptors so the body learns how to kill those proteins. a therapeutic doesn't want you to kill the proteins it creates because the proteins created need to be able to…
Thanks. If I'm correct then the mRNA vaccine introduces proteins that reflect the virus and trigger the immune response? I think I was reading the article as mostly focused on vaccines, but it was focused on cancer treatment, hence my confusion...
You're about right. the mRNA vaccine introduces mRNA, which is taken up by cells. The cells then use the mRNA to produce the proteins of interest, which then can be presented to immune cells to start the immune response.
mRNA is sort analogous to code that compiles to proteins
> 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.
"The New York Times warns that a particle of carfentanil as small as a grain of salt or piece of dust can be deadly and that the drug is lethal in a dose as minuscule as 0.02 milligrams. "
so about 1/50th of a milligram is deadly... not sure what's the maximum dose before it kills you
> mRNA can only be used to make the body make proteins that, well, the body can make. This might seem obvious, but it’s a pretty key part of where Moderna’s “software of life” analogy falls flat. It’s a limited software with limited toolkits. You’re not going to use mRNA in humans to make, say, an antibiotic that’s naturally produced in fungi.
Hmm? I keep hearing about plants and bacteria that have been genetically modified to secrete e.g. animal proteins. Do fungi assemble their proteins from a different set of amino acids than animals do?
> 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).
You're talking about opportunity cost, I don't know enough to speak to that, but that there is something else just as good or better doesn't make it any lesser.
At this point, the author of this article is more expert than I'll ever be, I'd assume that he has reasons to consider mRNA a low hanging fruit compared to existing tech like protein-subunit or adenovirus for infectious diseases.
And against DNA-based, well mRNA has beat it to the punch in being used at scale in humans, so that's possibly one advantage.
> mRNA can only be used to make the body make proteins that, well, the body can make. This might seem obvious, but it’s a pretty key part of where Moderna’s “software of life” analogy falls flat. It’s a limited software with limited toolkits. You’re not going to use mRNA in humans to make, say, an antibiotic that’s naturally produced in fungi. Hmm? I keep hearing about plants and bacteria that have been genetically m…
Antibiotics are not necessarily proteins but can be arbitrary ‘small molecules’ which could require a suite of enzymes instead of just one enzyme
> mRNA can only be used to make the body make proteins that, well, the body can make. This might seem obvious, but it’s a pretty key part of where Moderna’s “software of life” analogy falls flat. It’s a limited software with limited toolkits. You’re not going to use mRNA in humans to make, say, an antibiotic that’s naturally produced in fungi. Hmm? I keep hearing about plants and bacteria that have been genetically m…
Antibiotics are not necessarily proteins but can be arbitrary ‘small molecules’ which could require a suite of enzymes instead of just one enzyme