sanscript: Reminds me if that movie "splice". Awkward stuff ;P

sanscript: However, since we're dealing with propriety vaccines that are closed we have no idea what's in them, and, as you say about the long-term effects, so it's generally good to be cautious.

Tallima: The Pfizer vaccine doesn’t alter your DNA. You may want to reconsider your news sources.

malikhis: All I can guess is to ask the question of does an mRNA vaccine have the potential to cause "single cell mutations." The answer is PROBABLY yes (hence the theory) but instead of explaining the risk and helping people to understand it, the media just makes fun of it and hides it from others.

DarrkPhoenix: Mutagenicity is one of the earliest safety studies run in pharmaceutical development, and positive results there will stop a drug dead in its tracks. The Ames study is used to assess whether a compound is potentially mutagenic, and another study called a micronucleus study is used to assess whether a compound is capable of causing chromosomal damage. Other special cases are also evaluated early, such as assessing whether a compound is a potential teratogen (capable of causing birth defects). Because toxicology involving DNA damage/alteration and related effects can take a while to observe in a clinical setting (while also being quite horrific in their effects) it's assessed extremely rigorously before compounds even go into humans.

DarrkPhoenix: Science denier? I've got a masters degree in chemistry and have been working in pharmaceutical development for over a decade. One of the projects I worked on for the past several years is in the clinic for a COVID-related indication right now. This isn't some area where I'm just pontificating for the hell of it- this is something I live every day of my life.

The FDA needs to see mutagenicity safety data as part of every IND filing before they'll allow anything to be dosed to humans. There's no need to talk about general vaccines, or specifically the Pfizer or Moderna vaccines separately here, because they had to go through the same pre-clinical process as every other IND.

Also, the -70 C storage requirement for the Pfizer vaccine is not to prevent mutation, but chemical degradation. The Moderna vaccine, despite being very similar had a few changes made to increase the chemical stability, hence why the storage requirements for it aren't as stringent as for the Pfizer vaccine. Also, while I haven't seen any data released on this, I also expect Pfizer (or rather BioNTech) characterized the major degredants that formed at higher temperatures, and also likely ran several in vitro safety studies on several of them (at least this is what my team would have done in a similar position- or rather thermal stability and degradent characterization is what we do do as part of the pre-clinical work for any API).

Finding out that your drug is mutagenic after it's been approved and distributed is a catastrophic and extremely expensive failure, so pharma companies have every incentive to figure this out as early as possible. The FDA is also very sensitive when it comes to this kind of safety data, and if they're not satisfied with it they won't even let a compound go into the clinic.

Now, if you have any specific questions about the Pfizer or Moderna vaccines, the clinical and approval process, or anything else about vaccine or drug development, I'd be happy to provide answers to the best of my ability.

Abishia: but their is no denying that when you put Rna inside you, that you are altering your DNA local or global
chemistry can only do so much and is not persisted.

DarrkPhoenix: Science denier? I've got a masters degree in chemistry and have been working in pharmaceutical development for over a decade. One of the projects I worked on for the past several years is in the clinic for a COVID-related indication right now. This isn't some area where I'm just pontificating for the hell of it- this is something I live every day of my life.

DarrkPhoenix: Finding out that your drug is mutagenic after it's been approved and distributed is a catastrophic and extremely expensive failure, so pharma companies have every incentive to figure this out as early as possible. The FDA is also very sensitive when it comes to this kind of safety data, and if they're not satisfied with it they won't even let a compound go into the clinic.

DarrkPhoenix: The FDA needs to see mutagenicity safety data as part of every IND filing before they'll allow anything to be dosed to humans. There's no need to talk about general vaccines, or specifically the Pfizer or Moderna vaccines separately here, because they had to go through the same pre-clinical process as every other IND.

Abishia: I dont think the mRNA vaccines are cancerous (what a name) or any virus would already wiped out humanity like ages ago.

but their is no denying that when you put Rna inside you, that you are altering your DNA local or global
chemistry can only do so much and is not persisted.

anzial: you worry about changes to your DNA? then you got to stop living, period. DNA changes over the lifetime of a person. When you are 30, your DNA is not the same as when you were 1 year old. As Willard Motley wrote almost a 100 years ago: "Live fast, die young, and have a good-looking corpse"

DarrkPhoenix: Alright, let's talk specifics about RNA stability and the vaccine's stability in particular. I'm going to go a bit heavy on the chemical biology here, so if you need clarification on things feel free to ask. RNA is composed of sub-units (nucleotides) that consist of one of four bases (guanine, uracil, cytosine, adenine) linked to a sugar (ribose). The ribose portions of these sub-units are then linked together by phosphate groups via the 3' and 5' hydroxyl groups on each ribose, essentially making a polymer of the phospho-ribose sub-units that's used to present a sequence of bases. This sequence of bases is what's used to encode genetic information for protein construction. This is similar to DNA, with the differences of 1) DNA uses deoxyribose instead of ribose (the 2' hydroxyl group is missing) 2) DNA uses the thymine base in place of uracil and 3) DNA is double-stranded while RNA is typically single-stranded in a biological setting.

The challenge working with RNA is that it's inherently a very unstable molecule. The primary mode of degradation is hydrolysis of the phosphoester linkages, either by water (if in an aqueous environment) or self-hydrolysis via the 2'-hydroxy group that's proximal to the phosphate center (this group is positioned to attack the phosphorous center to make a 5-membered ring, which is kinetically high favored). In vivo RNA is not intended to stick around for very long (it gets transcribed, does its business, then enzymes start chewing it up) so this isn't an issue, but for mRNA vaccines that need to be stored for a while this presents a major issue. It should be noted that DNA doesn't have this issue with stability as 1) it's missing the 2'-hydroxyl group needed for self-hydrolysis and 2) the double-stranded structure confers significant stability to hydrolysis via conformational constraint.

Keeping the temperature low is the simplest way of stopping RNA from degrading (lowering the temperature sufficiently makes it so a given chemical reaction can't get over the energy barrier of its transition state). It's interesting to note, however, the less stringent temperature requirements for the Moderna vaccine vs the Pfizer vaccine. Moderna hasn't yet published on the reason for this, but in their press releases they've attributed it to the lipid nanoparticle encapsulation of the mRNA. Both BioNTech (partnered with Pfizer) and Moderna used lipid nanoparticles as an essential part of their vaccines (this was what made the mRNA approach actually viable), but it seems like Moderna's lipid nanoparticle technology is better at stabilizing the RNA. I suspect this is due to their technology either excluding water better from the interior of the nanoparticles, or restricting the conformation of the RNA strand in a way that confers stability to self-hydrolysis, but we'll need to wait for their publications to know for sure.

So that's a very brief background on RNA stability, which brings us to the central topic of what happens if some level of degradation does occur. In such a case the RNA sequence is basically chopped into multiple fragments, so if taken up by a ribosome will only produce a portion of the SARS-CoV-2 spike protein. However, only the portion with the original 5' end of the sequence will be able to do this- this is due to a regulatory mechanism in the ribsomal complex that looks for what's called the 5' untranslated region (5'-UTR), followed by a start codon (a specific 3-base sequence, usually AUG) before it will start translating a piece of mRNA into a protein. So even if the original mRNA degrades into 20+ pieces only one of those will get translated into a starting fragment of the spike protein. Eventually all of the mRNA fragments will be metabolized to the individual nucleotides, which will then get recycled into other RNA strands that our cells are constantly producing and destroying. The incomplete spike protein will ultimately get metabolized as well- there's plenty of cellular machinery dedicated to breaking down proteins and protein fragments that aren't recognized. If enough of a specific spike protein fragment forms it could potentially also trigger an immune response, but it is highly unlikely that a specific fragment will form in high enough amounts for this if it's just due to chemical cleavage at random points along the RNA chain. It should also be noted that mRNA degradation is something that also happens naturally with our own mRNA, so having protein fragments form from such a case is nothing new to our cells.

Also, since your concern seemed to center specifically around cancer, note that this requires modification or damage of a cell's DNA, and as I earlier explained to another poster the mRNA vaccines are not designed to modify DNA, are not designed to even enter the nucleus, and tested to make sure the components don't unintentionally damage DNA. So we're left with a vaccine that has been tested for mutagenicity (and found to not cause any), and for which no plausible mechanism has been proposed by which it may cause DNA damage. Now, if you have a specific mechanism in mind that you're concerned about I'd be happy to discuss it, but if your worry stems solely from RNA being kinda like DNA, and DNA being something you know is somehow related to cancer, and since you don't understand details beyond that that's good enough for you... well, in that case there's not really much else to discuss.

Now, if there are any questions I'd be happy to try to answer them.