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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

#31

Post by didibus »

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?

> Why are we assuming success already?

I guess a combination of how little side-effects they've had at scale, and of how effective the data shows they are at preventing the first virus and the earlier variants, which is what it was designed for.

I think the uptick expected is with regards to unvaccinated people, and to new variants for the most part. You should also still see a 5% to 10% of cases in vaccinated people, as the vaccines show a range of effectiveness only around the 90%, so an uptick will still occur, but the overall numbers should be much lower in vaccinated people.

To conclude, success is not on our fight against Covid, though you can say it definitely helped a lot, but the vaccine technology has definitely shown success here.

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

#32

Post by SV_BubbleTime »

nabla9 wrote: post #13
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

His "Things I Won’t Work With" articles are really informative and entertaining. https://blogs.sciencemag.org/pipeline/archives/category/thin... For example: Things I Won’t Work With: Dioxygen Difluoride https://blogs.sciencemag.org/pipeline/archives/2010/02/23/th...

> If the paper weren’t laid out in complete grammatical sentences and published in JACS, you’d swear it was the work of a violent lunatic.

Favorite part of a good article. Although it seems to me these experiments need to be repeated, for science.

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

#33

Post by seaman1921 »

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.

> Your body is good at dealing with foreign proteins.

Not always - Are you familiar with Prions diseases ?

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

#34

Post by GuB-42 »

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…

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.

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

#35

Post by seaman1921 »

XorNot wrote: post #30
TeMPOraL wrote: post #22

Earlier quoted context omitted.

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.

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 ?

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

#36

Post by landryraccoon »

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. It's hard to come up with a meaningful therapeutic in such a small amount of material.

I'm going to echo others and ask what you mean here. A lot of drugs have effective doses lower than 30mg. Are you saying that 30mg is an unusually small dose for a pharmaceutical? Because I don't think that's true.

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

#37

Post by lnwlebjel »

wahern wrote: post #8
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?

What's the replication accuracy of SARS-CoV-2?

At least 95% I would wager

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

#38

Post by redis_mlc »

maxerickson wrote: post #29
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.

Or, you know, corona is a highly contagious disease and after a year we've reached herd immunity in the US. Which is basically what the NIH just reported on June 22, 2021:

https://www.nih.gov/news-events/news-releases/nih-study-sugg...

The NIH report debunks two common tropes on HN:

1) That consumer masks work - they don't stop the spread of corona.

2) That COVID-19 vaccines are necessary for herd immunity - we already had it beforehand.

This was obvious (and I mentioned that here several times) since early 2020 if you look at the Santa Clara hospital ICU utilization, which averaged only 10% throughout most of the pandemic because of daily flights from China to SFO causing widespread infections in SF and SC.

Sorry for reporting actual science (with data) on HN, instead of the garbage discussed here since early 2020. My bad.

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

#39

Post by swlp21 »

GuB-42 wrote: post #34
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…

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.

I don't think it is correct to say only one drug is measured in µg.

Levothyroxine (for underactive thyroid) is typically administered in µg doses - but patient confusion with the more common mg means most medical staff will translate any mg dose a patient claims to be taking to µg automatically.

It may be atypical, but it's certainly not rare for drugs to be µg doses.

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

#40

Post by fastaguy88 »

tgb wrote: post #12
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.

What error correction does RNA have? Are you just referring to the third base in the codons? DNA has some but I don't know of any for RNA, and it hardly seems worth it for most organisms to have RNA error-correction: it's better to just degrade the RNA and retranscribe it.

RNA and DNA essentially use the same genetic code, which is degenerate and thus somewhat error correcting.
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