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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

#81

Post by manwe150 »

thaumasiotes wrote: post #77

> 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…

I don’t see that exact quote, but the article seems to be a list of many of the reasons just inserting the same mRNA sequence may not work as desired. To compare contextually also, researchers now spend substantial effort to teach simple monocellular organisms to produce various proteins of interest, because the pathway and other influences in the cell can influence whether it is translated and how the protein folds.

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

#82

Post by passivate »

ummonk wrote: post #70
tiahura wrote: post #55

Earlier quoted context omitted.

“The mRNA vaccine seems to be highly effective, two doses of that vaccine against this variant,” Gottlieb said, referring to the Moderna and Pfizer/BioNTech vaccines. “The viral vector vaccines from J&J and AstraZeneca also appear to be effective, about 60% effective. The mRNA vaccines are about 88% effective.”

I'm talking about protein subunit and DNA-based technologies, not adenovirus viral vector. Protein subunit vaccines at least (e.g. the novavax and GSK vaccines) have proven themselves against COVID-19 as well.

Just to clarify, a DNA based vaccine needs a platform/vector, which is what the adenovirus is. The viral vector is not a vaccine by itself.

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

#83

Post by G3rn0ti »

thaumasiotes wrote: post #77

> 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…

Plants and bacteria lack an immune system like the human‘s. Fully fledged immune systems with antibodies, T killer cells and B memory cells is something mammals „invented“.

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

#84

Post by manwe150 »

headsoup wrote: post #71
DaniloDias wrote: post #68

Earlier quoted context omitted.

[flagged]

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.

If he wrote instead of “does it prevents death? Perhaps.” actual estimated numbers, I think the question would be clearer: “is 300000 bigger than 6000? Perhaps.”

But that “Perhaps” seems to be doing a lot of work there, which would normally be done by words such as “So far quite well”

Has any of their claims ever happened before? Random internet dude would benefit from offering some links to past examples, or his questions sound like he hasn’t done any honest attempt at research, but just made them up like a fairy tale villain.

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

#85

Post by logicchains »

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.

A nice presentation by the FDA about why they're reluctant to let new treatments through without full phase 3 trials: https://www.fda.gov/about-fda/reports/22-case-studies-where-...

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

#86

Post by tjpnz »

DaniloDias wrote: post #68
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?

[flagged]

>Does it prevent deaths? Perhaps. It appears to cause deaths too.

That data doesn't necessarily establish a causal link between the vaccine and death.

Visiting a health care facility for instance already puts you at increased risk of a bacterial infection. Which is why I always take a long shower after.

If there is a direct connection with the vaccine how many of those people had a preexisting health condition that should've made them ineligible to receive it?

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

#87

Post by passivate »

thaumasiotes wrote: post #77

> 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…

> 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?

You're correct that the genetic code is _almost_ universal, and we do use mammalian expression platforms without problems. However, using a live human to express a protein that we normally never do is a bit of an ethical problem due to the associated risk. You don't want a partial expression or maybe a protein gets cleaved and turns into a toxin, or is misfolded and then ends up killing the host or causing a fatal disease (hello prions!), etc, etc.

(Source: Just stuff I picked up at work, I'm not an expert on these topics)

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

#88

Post by caf »

This sort of mRNA work isn’t immune-driven at all, in theory, and if you need your target cells to keep producing your desired protein, you’re going to have to keep telling them that by sending them more mRNA. Once a day? Once a week? Who knows? That’ll need to be worked out by experiment.

This doesn't seem like a problem from the point of view of those who are in the business of selling mRNA :)

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

#89

Post by vinay427 »

G3rn0ti wrote: post #83
thaumasiotes wrote: post #77

> 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…

Plants and bacteria lack an immune system like the human‘s. Fully fledged immune systems with antibodies, T killer cells and B memory cells is something mammals „invented“.

Your point of course stands, but from what I can tell (as someone very much not an expert, i.e. glad to be corrected), the history of the adaptive immune system is far more continual and definitely precedes mammals, with the "fully-fledged" versions found in early vertebrates and some mechanisms preceding that as well.

The abstract here seems quite well-written: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919748/

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

#90

Post by wbl »

logicchains wrote: post #85
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.

A nice presentation by the FDA about why they're reluctant to let new treatments through without full phase 3 trials: https://www.fda.gov/about-fda/reports/22-case-studies-where-...

We don't do phase III trials for the flu vaccine every year. Instead we follow the same production formula for the new virus variant. Why not with COVID? The FDA agrees this is desirable but is just foot dragging.
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