4 ms·

mRNA vaccines like the Pfizer and Moderna COVID vaccines don't enter the nucleus nor have a permanent effect. The mRNA breaks down after a few days.

stefantalpalaru 1y ago
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msandford 1y ago
Do we have any studies that show this fast clearance? From what I understand at least one of them used a pseudo-uradine that there isn't an efficient direct metabolic pathway to process, which was kind of the whole point. The idea being it would circulate longer and be "more effective"
- leereeves 1y ago
  That's right, they use N1-Methylpseudouridine instead of uridine (the nucleoside contained in uracil, which is the U in mRNA sequences) to last a bit longer (but not forever) and to avoid triggering immune reactions to the mRNA itself (the immune system can detect foreign mRNA). Certainly the vaccine's mRNA sequence breaks down into separate nucleotides. If it did not, continued production of the antigens would cause a chronic immune reaction and/or immune exhaustion that would make the vaccine ineffective. I don't know what happens to the N1-Methylpseudouridine though. That's an interesting question.
  - msandford 1y ago
    > Certainly the vaccine's mRNA sequence breaks down into separate nucleotides. If it did not, continued production of the antigens would cause a chronic immune reaction and/or immune exhaustion that would make the vaccine ineffective. I suspect you just described "long COVID" or "vaccine injury" for some fraction of folks.
    - amy_petrik 1y ago
      Also, people are usually like LOL it's just mRNA it goes away But evidence does show it CAN go back to DNA with mechanisms familiar to anyone edgycated in molecular genetics - https://pubmed.ncbi.nlm.nih.gov/35723296/ https://pubmed.ncbi.nlm.nih.gov/35723296/ Now, that particular study is in whatever cell line, highly dubious how it pertains to a human body, a few steps removed. But if you say "will you see this if you vaccinate 500 million times in 500 million people each with 500 trillion cells" - yea probably you would
- puzzlingcaptcha 1y ago
  The uridine modification was intended to reduce immunogenicity of mRNA - some of our immune cells have pattern-seeking receptors in the TLR family that recognize ssRNA and dsRNA. The presence of modified uridines throws this pattern recognition off. (https://doi.org/10.1016/j.jconrel.2015.08.051 https://doi.org/10.1016/j.jconrel.2015.08.051) The modifications to increase mRNA half-life concerned mostly the caps and poly(A) tail. But even with those the persistence was in the range of days (sort of depending on how sensitive a method you picked).
- justsee 1y ago
  Numerous studies have found vax-derived spike persisting for months and even years after vaccination, giving rise to concerns expression of spike can continue long after the claimed 24-48 hours. A recent study found spike protein persisting for 17 months in the cerebral arteries of stroke victims. [1] [1] https://www.sciencedirect.com/science/article/pii/S096758682500195X https://www.sciencedirect.com/science/article/pii/S096758682...
  - leereeves 1y ago
    That is interesting, but the authors point out: > In our study, in situ hybridization detected both mRNA derived from the vaccine and mRNA from the SARS-CoV-2 virus. ... our in situ hybridization method has high sensitivity and could detect trace amounts of mRNA, possibly reflecting unrecognized asymptomatic infections. These findings emphasize the need for caution in interpreting the presence of spike protein as exclusively vaccine-related. We should also note that the study doesn't show that the original vaccine mRNA somehow survived for months, only that mRNA matching the vaccine sequence was detected by complementary probes. I wonder if, in these cases, the vaccine was administered to someone with an active (but asymptomatic) COVID infection, and the vaccine mRNA was copied by the same RNA-dependent RNA polymerase that copies the viral RNA. That might explain why both vaccine and viral RNA were found.

stefantalpalaru 1y ago

[dead]

msandford 1y ago

Do we have any studies that show this fast clearance? From what I understand at least one of them used a pseudo-uradine that there isn't an efficient direct metabolic pathway to process, which was kind of the whole point. The idea being it would circulate longer and be "more effective"

leereeves 1y ago
That's right, they use N1-Methylpseudouridine instead of uridine (the nucleoside contained in uracil, which is the U in mRNA sequences) to last a bit longer (but not forever) and to avoid triggering immune reactions to the mRNA itself (the immune system can detect foreign mRNA). Certainly the vaccine's mRNA sequence breaks down into separate nucleotides. If it did not, continued production of the antigens would cause a chronic immune reaction and/or immune exhaustion that would make the vaccine ineffective. I don't know what happens to the N1-Methylpseudouridine though. That's an interesting question.
- msandford 1y ago
  > Certainly the vaccine's mRNA sequence breaks down into separate nucleotides. If it did not, continued production of the antigens would cause a chronic immune reaction and/or immune exhaustion that would make the vaccine ineffective. I suspect you just described "long COVID" or "vaccine injury" for some fraction of folks.
  - amy_petrik 1y ago
    Also, people are usually like LOL it's just mRNA it goes away But evidence does show it CAN go back to DNA with mechanisms familiar to anyone edgycated in molecular genetics - https://pubmed.ncbi.nlm.nih.gov/35723296/ https://pubmed.ncbi.nlm.nih.gov/35723296/ Now, that particular study is in whatever cell line, highly dubious how it pertains to a human body, a few steps removed. But if you say "will you see this if you vaccinate 500 million times in 500 million people each with 500 trillion cells" - yea probably you would
puzzlingcaptcha 1y ago
The uridine modification was intended to reduce immunogenicity of mRNA - some of our immune cells have pattern-seeking receptors in the TLR family that recognize ssRNA and dsRNA. The presence of modified uridines throws this pattern recognition off. (https://doi.org/10.1016/j.jconrel.2015.08.051 https://doi.org/10.1016/j.jconrel.2015.08.051) The modifications to increase mRNA half-life concerned mostly the caps and poly(A) tail. But even with those the persistence was in the range of days (sort of depending on how sensitive a method you picked).
justsee 1y ago
Numerous studies have found vax-derived spike persisting for months and even years after vaccination, giving rise to concerns expression of spike can continue long after the claimed 24-48 hours. A recent study found spike protein persisting for 17 months in the cerebral arteries of stroke victims. [1] [1] https://www.sciencedirect.com/science/article/pii/S096758682500195X https://www.sciencedirect.com/science/article/pii/S096758682...
- leereeves 1y ago
  That is interesting, but the authors point out: > In our study, in situ hybridization detected both mRNA derived from the vaccine and mRNA from the SARS-CoV-2 virus. ... our in situ hybridization method has high sensitivity and could detect trace amounts of mRNA, possibly reflecting unrecognized asymptomatic infections. These findings emphasize the need for caution in interpreting the presence of spike protein as exclusively vaccine-related. We should also note that the study doesn't show that the original vaccine mRNA somehow survived for months, only that mRNA matching the vaccine sequence was detected by complementary probes. I wonder if, in these cases, the vaccine was administered to someone with an active (but asymptomatic) COVID infection, and the vaccine mRNA was copied by the same RNA-dependent RNA polymerase that copies the viral RNA. That might explain why both vaccine and viral RNA were found.