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What is this trying to say? That the actual "blueprint" plasmid DNA -- from which the vaccine RNA is generated -- leaks into the vaccine during the manufacturin

What is this trying to say? That the actual "blueprint" plasmid DNA -- from which the vaccine RNA is generated -- leaks into the vaccine during the manufacturing process? Or is it saying that other DNA from the bacterial vector (Escherichia coli) gets into the vaccine? Ok, say that happened. What would the consequences be? AIUI, both vaccines use a special lipid "bubble" around the RNA (and I suppose this accidental DNA) to get it through cell walls. Once in the cell, the RNA then gets to work, instructing the cell to start manufacturing various proteins from the COVID-19 virus -- most notably the spike protein. But suppose that some DNA also makes it inside. What happens to it? Hypothetically, can it encounter DNA polymerase there and start replicating? Would it be transcribed to RNA and would it start making proteins? I understand that extrachromosomal DNA (mostly mitochondrial DNA) does exist and is heritable, almost only from the mother. Would this get into oocytes? But presumably DNA from viruses is not hugely different, and we constantly encounter viruses. And yes there's some gene transfer that happens occasionally but somehow this isn't generally a big deal? (I guess sometimes it results in cancer? I'm assuming that's the mechanism behind, say, HPV?) So maybe some kind of long term consequences are conceivable, but, probably not, thanks to our immune systems? So maybe this would cause some inflammation until the immune system mopped it up, and that'd be all? I'm just trying to think this through. I'd like to hear spelled out exactly what the implications supposedly are. I don't just want to hear "Booo! Scary DNA!", I want to hear a plausible explanation for why it might matter.

fasteo 3y ago
>>> I'd like to hear spelled out exactly what the implications supposedly are We do not know, and that's precisely the problem
nvm0n2 3y ago
Foreign DNA that gets into your cells can be integrated into your own DNA, meaning indefinite spike protein production and consequent immuno-tolerance. This is likely the explanation for the (not media reported) cases where people who got vaccinated start testing PCR positive indefinitely, or who still test positive for spike weeks after the shot when it's supposed to dissipate within days. It may also explain many of the nasty side effects and injuries. > presumably DNA from viruses is not hugely different It's pretty different yeah. The RNA/DNA in the vaccines is hyper-optimized to produce spike relative to anything nature would produce, and the pseudouridine stops the immune system detecting and destroying it as it normally would with viral RNA. So the immune system isn't going to find it easy to mop this up, the vaccine is specifically engineered to avoid that (otherwise the mRNA wouldn't reach your cells at all).
- shadowgovt 3y ago
  > So the immune system isn't going to find it easy to mop this up The immune system is extremely good at cleaning up unencapsulated DNA and the pseudouridine is not intended to prevent that.
  - nvm0n2 3y ago
    The DNA isn't unencapsulated, is it? It's inside the lipid nanoparticles that are designed to enable transfection. And the pseudouridine is there specifically to disable the immune system's usual responses.
dekhn 3y ago
My experience in this area is quite dated, I don't want to give the impression I'm truly an expert in this area. My guess- based on a few decades of working with DNA and RNA and proteins, is that it's unlikely a small amount of unintentional DNA in a vaccine would cause any detectable harm. The argument is basically that the DNA would have to have very specific sequence to be transcribed by DNA Polymerase to RNA, the resulting RNA would need to have a very specific sequence to be translated, and to avoid being detected as foreign RNA (cells have a robust collection of tools to dice up invading DNA). And I agree that the resulting proteins- even if through some extremely improbable event led to a small number of peptides or protein fragments were expressed, they would be "mopped up by the immune system", with some inflammation, as you say. Witha ll that said I'm sure you can find examples of people who set up cellular experiments that demonstrated some injected DNA could be expressed, as biology is ultimately a probabilistic and stochastic system and there's always some level of nonspecific behavior that can't be ruled out.

fasteo 3y ago

>>> I'd like to hear spelled out exactly what the implications supposedly are We do not know, and that's precisely the problem

nvm0n2 3y ago

Foreign DNA that gets into your cells can be integrated into your own DNA, meaning indefinite spike protein production and consequent immuno-tolerance. This is likely the explanation for the (not media reported) cases where people who got vaccinated start testing PCR positive indefinitely, or who still test positive for spike weeks after the shot when it's supposed to dissipate within days. It may also explain many of the nasty side effects and injuries. > presumably DNA from viruses is not hugely different It's pretty different yeah. The RNA/DNA in the vaccines is hyper-optimized to produce spike relative to anything nature would produce, and the pseudouridine stops the immune system detecting and destroying it as it normally would with viral RNA. So the immune system isn't going to find it easy to mop this up, the vaccine is specifically engineered to avoid that (otherwise the mRNA wouldn't reach your cells at all).

shadowgovt 3y ago
> So the immune system isn't going to find it easy to mop this up The immune system is extremely good at cleaning up unencapsulated DNA and the pseudouridine is not intended to prevent that.
- nvm0n2 3y ago
  The DNA isn't unencapsulated, is it? It's inside the lipid nanoparticles that are designed to enable transfection. And the pseudouridine is there specifically to disable the immune system's usual responses.

dekhn 3y ago

My experience in this area is quite dated, I don't want to give the impression I'm truly an expert in this area. My guess- based on a few decades of working with DNA and RNA and proteins, is that it's unlikely a small amount of unintentional DNA in a vaccine would cause any detectable harm. The argument is basically that the DNA would have to have very specific sequence to be transcribed by DNA Polymerase to RNA, the resulting RNA would need to have a very specific sequence to be translated, and to avoid being detected as foreign RNA (cells have a robust collection of tools to dice up invading DNA). And I agree that the resulting proteins- even if through some extremely improbable event led to a small number of peptides or protein fragments were expressed, they would be "mopped up by the immune system", with some inflammation, as you say. Witha ll that said I'm sure you can find examples of people who set up cellular experiments that demonstrated some injected DNA could be expressed, as biology is ultimately a probabilistic and stochastic system and there's always some level of nonspecific behavior that can't be ruled out.