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

blogs.sciencemag.org

121–130 of 152 posts

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

#121
post #16

When it comes to the problem of targeting, one interesting and promising tech is photochemical internalisation [ https://en.m.wikipedia.org/wiki/Photochemical_internalizatio... ], where you put the mRNA inside photosensitive molecules (and not lipids) and then shine some light on the tissue/organ where you want the mRNA delivered. Where activated by the light, the molecules then enter the cells, dissolves and deliver…

[deleted]

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

#122
post #20

Earlier quoted context omitted.

> 30 mg is really tiny Not really. For example the amount of beta blocker I take for my heart problems is 5mg per day - the pill size goes down to 2.5mg.

Pretty sure they meant micrograms, not milligrams.

Then they should not have used the SI milli- prefix.

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

#123

Earlier quoted context omitted.

> In eg German, people generally differentiate between Medikamente and Drogen, but they still have a Drogerie which is essentially the same as a drug store. To add a little additional context 'Drogerie' mostly sells hygiene products, supplements and the like. They only sell 'Medikamente' which are allowed to be sold over the counter in Germany, which basically is Aspirin and everything that is even more harmless. You…

> 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.

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

#124

Earlier quoted context omitted.

mRNA vaccines are not "hugely outperforming other technologies in COVID". Sputnik V has around the same efficacy after 1 dosis that Biontech has after 2. That's 1-0 for Sputnik in my book.

Aaaaand here come the downvotes from the adherents of the religion of mRNA Technology :D Scientific objectivity is LONG GONE! "With the Pfizer/BioNTech vaccine, protection against symptomatic COVID-19 was found to be 52% from 12 days after the first dose (immunity takes time to build). Protection then rose to 95% after the second dose." [1] "Vaccine efficacy, based on the numbers of confirmed COVID-19 cases from 21 d…

AZ is not a mRNA vaccine.

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

#125

Earlier quoted context omitted.

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).

Eventually the capsule will break down, be filtered out or be destroyed by the immune system and any RNA left will be broken down by RNAse.

More info about RNA destruction and RNAse https://en.wikipedia.org/wiki/Ribonuclease

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

#126
post #105
post #98

Earlier quoted context omitted.

Drugs having to be government approved is a relatively recent development. Perhaps about a hundred years, give or take. See https://en.wikipedia.org/wiki/International_Opium_Convention The English language just hasn't caught on, yet. At least not completely. In eg German, people generally differentiate between Medikamente and Drogen, but they still have a Drogerie which is essentially the same as a drug store.

'Medicine'? 'Medications'? 'Prescriptions'? I'd say 'drugs' does lean quite strongly towards the illicit kind. If a doctor asked me if I was 'taking any drugs', I would assume they wanted to know in confidence about anything recreational; not prescriptions/off the shelf medicine.

Yes, it depends on context.

Eg if your wife asks you whether you've taken your drugs yet, she means the same thing as meds.

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

#127

Earlier quoted context omitted.

mRNA vaccines are not "hugely outperforming other technologies in COVID". Sputnik V has around the same efficacy after 1 dosis that Biontech has after 2. That's 1-0 for Sputnik in my book.

Aaaaand here come the downvotes from the adherents of the religion of mRNA Technology :D Scientific objectivity is LONG GONE! "With the Pfizer/BioNTech vaccine, protection against symptomatic COVID-19 was found to be 52% from 12 days after the first dose (immunity takes time to build). Protection then rose to 95% after the second dose." [1] "Vaccine efficacy, based on the numbers of confirmed COVID-19 cases from 21 d…

Perhaps because of https://blogs.sciencemag.org/pipeline/archives/2021/04/28/ru...

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

#128
post #66

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…

Everyone seems to be focusing on your first comment at the dose must to be limited to 30 µg to avoid lipid toxicities. But the second issue is an even bigger issue—-the immune system will remove cells expressing proteins not found in the patient’s genome.

Under what circumstances does this occur? Is this something the cell itself signals to the immune system?

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

#129
post #11

Worth noting that even if it's good for literally only infectious disease vaccines, we're still taking about an enormous breakthrough with the potential to save hundreds of millions of lives. Imagine vaccines for malaria, HIV, Zika, and many others.

While mRNA vaccines were great in the COVID situation, they have been in development over the last decade and I'm not sure an HIV vaccine will be as simple as putting HIV envelope protein into this technology. I'm not aware of attributes to the mRNA technologies that will dramatically simplify the development challenges. I believe the more substantial step for is that we (Pharma, Investors, Governments)now realize infectious diseases are a problem for people beyond the developing world. Will that commitment hold?

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

#130
post #66

Earlier quoted context omitted.

Everyone seems to be focusing on your first comment at the dose must to be limited to 30 µg to avoid lipid toxicities. But the second issue is an even bigger issue—-the immune system will remove cells expressing proteins not found in the patient’s genome.

Under what circumstances does this occur? Is this something the cell itself signals to the immune system?

it's one of the most extraordinary details I've learned in biology. The thymus expresses cell types from around the body and trains the immune system to not recognize them as foreign:

https://en.wikipedia.org/wiki/Central_tolerance

it's not for genes, but for epitopes

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