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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

#131

Post by dekhn »

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…

the statement as written is not specific enough to be useful. We certainly have moved genes and entire synthetic pathways between organisms.

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

#132

Post by seaman1921 »

XorNot wrote: post #46
seaman1921 wrote: post #35

Earlier quoted context omitted.

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 coding is already something we carry, they're conformational jumps

Aha, this is helpful. And I believe mRNAs are not known to trigger these conformational jumps.

Another fact-check article supporting your statement: https://www.reuters.com/article/fact-check-no-evidence-that-...

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

#133

Post by ummonk »

passivate wrote: post #82
ummonk wrote: post #70

Earlier quoted context omitted.

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.

Yeah, good clarification. I should be saying DNA plasmid.

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

#134

Post by ummonk »

didibus wrote: post #78
ummonk wrote: post #47

Earlier quoted context omitted.

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 m…

I don't think he said that mRNA is low hanging fruit though. I think he said that vaccines for viral diseases are a low hanging fruit for applying mRNA.

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

#135

Post by gus_massa »

dragonwriter wrote: post #27
gus_massa wrote: post #26

Earlier quoted context omitted.

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.

I know... I know... You are right.

But a simple calculation sometimes is better than a correct long calculation in an online discussion :)

The correct calculation is to ask them "How sure are you that is at lest safe for X% of the persons?" The replies are like

100% sure that it's safe for 90% of the persons.

Also 100% sure that it's safe for 99% of the persons.

97% sure that it's safe for 99.9% of the persons.

93% sure that it's safe for 99.99% of the persons.

87% sure that it's safe for 99.999% of the persons.

...

Now you take the derivative of the function (or the inverse of the function?), multiply by -1 if necessary and get a gut feeling probability distribution to use to calculate the integral and get the expected values of deaths of using the new version without a clinical trial.

Anyway, you need a lot of 9s, because a FDA approval means almost automatic approval in a lot of countries. There are like 10 vaccines now and 7.000 million people in the word, so my guess that it will be used in 500-100 million people.

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

#136

Post by passivate »

unanswered wrote: post #114
passivate wrote: post #87

Earlier quoted context omitted.

> 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 p…

> 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 Wait, so are you saying there's an ethical problem with triggering the expression of a strictly viral protein known to cause damage in and of itself?

>Wait, so are you saying there's an ethical problem with triggering the expression of a strictly viral protein known to cause damage in and of itself?

:) We're discussing the expression of therapeutics. But, it is true that if you could control the process there would be no ethical problem. But it never is so simple. The cute analogies and diagrams (I do think they are useful for beginners) don't convey the real risks of the technology. Its really hard to wrap your brain around it, at-least for me, even after working in vaccines for close to a decade now I can only grasp a very limited amount of the complexity of our internals.

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

#137

Post by passivate »

ummonk wrote: post #133
passivate wrote: post #82

Earlier quoted context omitted.

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.

Yeah, good clarification. I should be saying DNA plasmid.

Yes, plasmids are the the most common, but there are many other methods too.

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

#138

Post by unanswered »

weinzierl wrote: post #123
unanswered wrote: post #112

Earlier quoted context omitted.

> I think there is no real distinction between drug store and pharmacy in English, but I'm not sure. This is... oversimplified, at least. I'm sure usage differs by region, even within the United States, but where I am a "drug store" is a convenience store which either contains or historically contained a pharmacy (in the latter case, there appears to be a decent chance the store is an historical soda fountain/cafe).…

Now that I read you comment I remember having seen this pharmacy within the drug store thing. I also remember that the lady there gave sort of medical advice to the customers and that I wondered if she was an MD or not.

That's a whole other discussion about the nature of pharmacies too. The pharmacists themselves have specific degrees and I always assume they're more knowledgeable about things like drug interactions than even the prescribing doctors, if that's the kind of medical advice you mean. One probably works with pharmacy technicians at the desk though; I'm not sure about their qualifications. At the very least the techs can help me find the right OTC medicine if I want it as drug stores tend to locate those strategically near the pharmacy.

But many US pharmacy chains also have RNs onsite providing services, part time, for vaccines and such. That's not quite the same as an MD but it's different than pharmacology.

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

#139

Post by thehappypm »

unanswered wrote: post #114
passivate wrote: post #87

Earlier quoted context omitted.

> 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 p…

> 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 Wait, so are you saying there's an ethical problem with triggering the expression of a strictly viral protein known to cause damage in and of itself?

There is, which is why it took so fucking long for these vaccines to get approved, they needed to be strenuously tested for safety and efficacy among tens of thousands of volunteers.

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

#140

Post by jhayward »

wbl wrote: post #90
logicchains wrote: post #85

Earlier quoted context omitted.

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.

Do you think there might be some difference in "changes each year for flu vaccine" and "changes for every other vaccine"?

Like perhaps, how much study the practice of flu vaccine changes has undergone, what the limited target constraints are, and prior field experience with the sterotypical changes to those specific targets?

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