7 ms·

Ebola, Malaria and HPV have working vaccines already, there's no particular need for new technology there. HIV would be interesting though. And bacteria aren'

Ebola, Malaria and HPV have working vaccines already, there's no particular need for new technology there. HIV would be interesting though. And bacteria aren't in general limited by immune response. The immune system has zero difficulty detecting a bacterial infection, but it happens at a wildly different scale and can't be fought with a fundamentally chemical means like our bodies do with virii. And the point about prions seems to misunderstand this technique. The way an mRNA vaccine works is by transmitting blueprints for a viral protein (but not the rest of the virus) into the body's cells, where ribosomes then synthesize the disembodied proteins, which get detected as "foreign invaders" and produce a lasting immune response which would then be effective against the real virus. Prions, remember, are just misfolded versions of your body's own proteins. They have the same sequence of amino acids as "correct" proteins and just an incorrect shape. mRNA only transmits the sequence, not the shape. And in any case your cell's DNA already has the sequence encoded, because you're not dead.

fabian2k 6y ago
The mRNA vaccines do also transmit the shape, as the encoded viral protein does get expressed in the cells. And the shape does get recognized by the immune system when that protein is secreted from the cell. But there is also a shape-independent mechanism that works on the sequence alone. The proteins in a cell are also chopped into tiny pieces and presentend on the surface. That part could not distinguish between different folded versions of the same protein like with prions.
- vlovich123 6y ago
  I think I was misunderstood a bit. I wasn't proposing that mRNA in its current state (or even solely by itself) would somehow be able to cure prion diseases. I was thinking more that research into biotech generally improves our knowledge. I don't know biology at all but I figured some evolution of technologies associated with CRISPR + mRNA + other things would be useful as a team in solving prion diseases. So maybe mRNA can become efficient enough that it's used to train the immune system to target the misfolded proteins themselves to try to limit damage while the treatment is ongoing. Futuristic now certainly, but is it definitely 100% impossible ever even as our knowledge & tech improves? Or maybe mRNA can exploit something in the prion process we don't yet understand. Maybe CRISPR could be part of the overall treatment therapy as you inoculate more of the body from whatever is propagating the bad code through your body which could be a time-consuming process (think vaccine at the genetic level - you potentially need to get it to every cell in the body). Obviously this is all sci-fi stuff & some of it impossible & out there. I still like to imagine sci-fi is useful as potential roadmaps to brainstorm how we might solve impossible problems - even if we miss, we'll land somewhere useful.
jcims 6y ago
Do prions typically occur because of a defect in the RNA or are there just certain protein structures that have instability in how they fold?
- type0 6y ago
  because the prions are chaperones, i.e they can fold other proteins
  - jcims 6y ago
    That’s how they turn your brain into Swiss cheese right? I’m just wondering how they are formed, are they misfolded normal proteins or just alien like virii.
    - bbojan 6y ago
      They are misfolded body's normal proteins, with a nasty side effect that they cause the normally folded copies of the same protein to also misfold in the same way. The result is a chain reaction of sorts.
- strbean 6y ago
  In my understanding, a defect in the RNA that affected the protein would necessarily result in a different amino acid sequence. So for prions to form, they would have to be misfolded initially due to chance / environment or re-arranged afterwards through some process. The best known protein to form prions (PrP, Prion Protein) is known to convert from the well-folded form to a misfolded form upon interacting with the misfolded form, which could indicate that spontaneous formation of prions is due to interaction with something after the initial folding. I think this could also just be an indication that PrP just has lots of very close low-energy states, which would mean a higher chance of misfolding initially. - Mostly lay person view (some bioinformatics experience)
  - deleted 6y ago
    [deleted]
rzwitserloot 6y ago
nitpick: virii is wrong. The latin plural of 'virus' does not exist. It is a nebulous, uncountable concept to ancient rome. Like 'malaise' or 'ocean' (we can pluralize oceans in english, but hopefully you can imagine that a language would treat it as a concept for which the concept of pluralization doesn't make sense). You'd think: Hey, it's `-us`, I know that one, it pluralizes to `-i`, but, no. There is no plural. It's a rare form that also ends in -us but doesn't work like most of the words you know derived from latin that end in -us. But there is `vir`, latin for 'man', and the plural of that is viri. So, 'viri', as in 'the latin pluralized form of virus', is dead wrong. There is no -ii ending in latin. At all. The plural of 'virus' in english is 'viruses'. Any other form is stupid. Sometimes language does that, but surely you'd agree that something like 'irregardless', whilst somewhat common, sounds very unprofessional. virii is the same way.
- thereisnospork 6y ago
  > There is no -ii ending in latin. At all. Triarii? (My knowledge of latin as a language comes primarily from Rome Total War).
- newacct583 6y ago
  Now that is an HN comment.
- admash 6y ago
  > There is no -ii ending in latin. At all. Should you mean no -ii ending to "virus" at all, it would appear to be a reasonable assertion. However if by "at all", you mean of any word in Latin, that is demonstrably false. http://latindictionary.wikidot.com/noun:filius http://latindictionary.wikidot.com/noun:filius Nominative and vocative plural: filii Usage example: "... et nihilo minus amicum gravem virum aut fidelem libertum lateri filii sui adiungere, ..." https://thelatinlibrary.com/quintilian/quintilian.institutio1.shtml https://thelatinlibrary.com/quintilian/quintilian.institutio...
- ink_13 6y ago
  I'll bet you 10 denarii you're wrong about suffixes.
flobosg 6y ago
> They have the same sequence of amino acids as "correct" proteins and just an incorrect shape. Somatic mutations can trigger the misfolding as well.
raducu 6y ago
Isn't HIV a special case though? The reason we don't have an HIV vaccine is because HIV embedds itself in the DNA of some cells and some of those cells don't start producing virions right away, the immune system can't detect them, you clear the visible infection, but just weeks after, those hidden cells start producing the virus and the infection starts over. So the issue with HIV is the hidden reservoir of infected cells, afik.

fabian2k 6y ago

The mRNA vaccines do also transmit the shape, as the encoded viral protein does get expressed in the cells. And the shape does get recognized by the immune system when that protein is secreted from the cell. But there is also a shape-independent mechanism that works on the sequence alone. The proteins in a cell are also chopped into tiny pieces and presentend on the surface. That part could not distinguish between different folded versions of the same protein like with prions.

vlovich123 6y ago
I think I was misunderstood a bit. I wasn't proposing that mRNA in its current state (or even solely by itself) would somehow be able to cure prion diseases. I was thinking more that research into biotech generally improves our knowledge. I don't know biology at all but I figured some evolution of technologies associated with CRISPR + mRNA + other things would be useful as a team in solving prion diseases. So maybe mRNA can become efficient enough that it's used to train the immune system to target the misfolded proteins themselves to try to limit damage while the treatment is ongoing. Futuristic now certainly, but is it definitely 100% impossible ever even as our knowledge & tech improves? Or maybe mRNA can exploit something in the prion process we don't yet understand. Maybe CRISPR could be part of the overall treatment therapy as you inoculate more of the body from whatever is propagating the bad code through your body which could be a time-consuming process (think vaccine at the genetic level - you potentially need to get it to every cell in the body). Obviously this is all sci-fi stuff & some of it impossible & out there. I still like to imagine sci-fi is useful as potential roadmaps to brainstorm how we might solve impossible problems - even if we miss, we'll land somewhere useful.

jcims 6y ago

Do prions typically occur because of a defect in the RNA or are there just certain protein structures that have instability in how they fold?

type0 6y ago
because the prions are chaperones, i.e they can fold other proteins
- jcims 6y ago
  That’s how they turn your brain into Swiss cheese right? I’m just wondering how they are formed, are they misfolded normal proteins or just alien like virii.
  - bbojan 6y ago
    They are misfolded body's normal proteins, with a nasty side effect that they cause the normally folded copies of the same protein to also misfold in the same way. The result is a chain reaction of sorts.
strbean 6y ago
In my understanding, a defect in the RNA that affected the protein would necessarily result in a different amino acid sequence. So for prions to form, they would have to be misfolded initially due to chance / environment or re-arranged afterwards through some process. The best known protein to form prions (PrP, Prion Protein) is known to convert from the well-folded form to a misfolded form upon interacting with the misfolded form, which could indicate that spontaneous formation of prions is due to interaction with something after the initial folding. I think this could also just be an indication that PrP just has lots of very close low-energy states, which would mean a higher chance of misfolding initially. - Mostly lay person view (some bioinformatics experience)
- deleted 6y ago
  [deleted]

rzwitserloot 6y ago

nitpick: virii is wrong. The latin plural of 'virus' does not exist. It is a nebulous, uncountable concept to ancient rome. Like 'malaise' or 'ocean' (we can pluralize oceans in english, but hopefully you can imagine that a language would treat it as a concept for which the concept of pluralization doesn't make sense). You'd think: Hey, it's `-us`, I know that one, it pluralizes to `-i`, but, no. There is no plural. It's a rare form that also ends in -us but doesn't work like most of the words you know derived from latin that end in -us. But there is `vir`, latin for 'man', and the plural of that is viri. So, 'viri', as in 'the latin pluralized form of virus', is dead wrong. There is no -ii ending in latin. At all. The plural of 'virus' in english is 'viruses'. Any other form is stupid. Sometimes language does that, but surely you'd agree that something like 'irregardless', whilst somewhat common, sounds very unprofessional. virii is the same way.

thereisnospork 6y ago
> There is no -ii ending in latin. At all. Triarii? (My knowledge of latin as a language comes primarily from Rome Total War).
newacct583 6y ago
Now that is an HN comment.
admash 6y ago
> There is no -ii ending in latin. At all. Should you mean no -ii ending to "virus" at all, it would appear to be a reasonable assertion. However if by "at all", you mean of any word in Latin, that is demonstrably false. http://latindictionary.wikidot.com/noun:filius http://latindictionary.wikidot.com/noun:filius Nominative and vocative plural: filii Usage example: "... et nihilo minus amicum gravem virum aut fidelem libertum lateri filii sui adiungere, ..." https://thelatinlibrary.com/quintilian/quintilian.institutio1.shtml https://thelatinlibrary.com/quintilian/quintilian.institutio...
ink_13 6y ago
I'll bet you 10 denarii you're wrong about suffixes.

flobosg 6y ago

> They have the same sequence of amino acids as "correct" proteins and just an incorrect shape. Somatic mutations can trigger the misfolding as well.

raducu 6y ago

Isn't HIV a special case though? The reason we don't have an HIV vaccine is because HIV embedds itself in the DNA of some cells and some of those cells don't start producing virions right away, the immune system can't detect them, you clear the visible infection, but just weeks after, those hidden cells start producing the virus and the infection starts over. So the issue with HIV is the hidden reservoir of infected cells, afik.