5 ms·

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-pharmaceuticals

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-pharmaceuticals/ 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 tiny. It's hard to come up with a meaningful therapeutic in such a small amount of material. People have been hyping up self-replicating mRNA as a solution, but that's still in its infancy, and has its own problems regarding the "compilers"/polymerases that need to be packaged with it.

zabzonk 5y ago
> 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.
- H8crilA 5y ago
  Not to mention LSD, which is a well below 1mg thing. Also not sure why it matters at all, if it's under 1g you can administer it pretty much any way you need to.
- FPGAhacker 5y ago
  Pretty sure they meant micrograms, not milligrams.
  - varjag 5y ago
    Then they should not have used the SI milli- prefix.
GuB-42 5y ago
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.
- swlp21 5y ago
  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.
  - krustyburger 5y ago
    I think the earlier commenter meant ‘drug’ as in street drug. But though that may have once been true, these days there are plenty of other designer drugs that come in tiny doses, many of them not as friendly as LSD.
    - Kiro 5y ago
      I don't understand why both are called drugs in English. My language also has the word "drugs" but it's used exclusively for street drugs.
      - eru 5y ago
        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 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.
        OJFord 5y ago
        '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.
landryraccoon 5y ago
> 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.
- TchoBeer 5y ago
  micrograms
deleted 5y ago
[deleted]
jostmey 5y ago
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.
- catlifeonmars 5y ago
  Under what circumstances does this occur? Is this something the cell itself signals to the immune system?
  - dekhn 5y ago
    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 https://en.wikipedia.org/wiki/Central_tolerance it's not for genes, but for epitopes

zabzonk 5y ago

> 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.

H8crilA 5y ago
Not to mention LSD, which is a well below 1mg thing. Also not sure why it matters at all, if it's under 1g you can administer it pretty much any way you need to.
FPGAhacker 5y ago
Pretty sure they meant micrograms, not milligrams.
- varjag 5y ago
  Then they should not have used the SI milli- prefix.

GuB-42 5y ago

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.

swlp21 5y ago
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.
- krustyburger 5y ago
  I think the earlier commenter meant ‘drug’ as in street drug. But though that may have once been true, these days there are plenty of other designer drugs that come in tiny doses, many of them not as friendly as LSD.
  - Kiro 5y ago
    I don't understand why both are called drugs in English. My language also has the word "drugs" but it's used exclusively for street drugs.
    - eru 5y ago
      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 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.
      - OJFord 5y ago
        '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.

landryraccoon 5y ago

> 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.

TchoBeer 5y ago
micrograms

deleted 5y ago

[deleted]

jostmey 5y ago

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.

catlifeonmars 5y ago
Under what circumstances does this occur? Is this something the cell itself signals to the immune system?
- dekhn 5y ago
  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 https://en.wikipedia.org/wiki/Central_tolerance it's not for genes, but for epitopes