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r/AskScienceDiscussion•
binaryice

What is the estimated number of mRNA sequences in a mCG of mRNA 1273?

They seem to list the Mrna as 100mcg per dose, and the NLPs as 1.93mg (1930mcg, right?) per dose.

The strand is 4000 nucleotides about, so thats' 330 daltons per base, and 1.3 x10^6 daltons per strand.

Would that imply that there are roughly 450 billion mRNA packets in a microgram, and 45trillion in a dose!?

official spec sheet data:

Moderna COVID-19 Vaccine is provided as a white to off-white suspension for intramuscular injection. Each 0.5 mL dose of Moderna COVID-19 Vaccine contains 100 mcg of nucleosidemodified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus. Each dose of the Moderna COVID-19 Vaccine contains the following ingredients: a total lipid content of 1.93 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.31 mg tromethamine, 1.18 mg tromethamine hydrochloride, 0.043 mg acetic acid, 0.20 mg sodium acetate trihydrate, and 43.5 mg sucrose.

Posted Sep 11, 2021, 8:59 PM UTC

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bobbot32•

Its hard to fathom the scale of how small things are but thats not out of the ordinary for medicine.

For reference at the scale of biochemistry, there are 9E20 molecules of ATP formed every second in a person which dwarves your number and thats per second. Biochemical scales have reeeally big numbers lol.

It is a lot compared to one cell sure but an entire tissue? Not that crazy. Its often overwhelming thinking about how much smaller and therefore how much more of something there often is

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binaryiceOP•

So you think my calculation is plausibly accurate?

I just assumed that you have a tiny fraction of your cells getting mRNA insertion, producing antigens, and pissing off the immune system.

I'd expected 0.1% of cells affected. Part of this is that I was assuming that in the process of the immune system creating a viable antibody, mass producing it, and bonding to the cells with a spike protein, the antibodies would act as flags for phagocytes, and the cells that receive the mRNA sequences would be destroyed by phagocytes.

Am I totally off base on the mechanistic response here? If not, it seems absurd that the dose of the vaccine would be 3 times as many mRNA sequences as the body has cells. That seems like it would be far too many cells getting flagged for phagocyte consumption.

I would be nonplussed by a total number of 50 billion, but 45 trillion just doesn't compute, considering my expectations of the vaccination process.

I know that the immune system is nuts, and that a single plasma cell or B cell or whatever makes some insane number of antibodies, I want to say it's 10^6 per minute or a number that just seems like it shouldn't be remotely possible, but obviously it's a battle against time to neutralize the infection in question before it ruins too many cells, but if the number of mRNA strands is accurate, what's happeneing with them? are you getting dozens of penetrations per cell near the injection site, and expressing hundreds of spikes per cell in some cases?

This just doesn't match with my cartoon version of cellular biology, so I'm trying to identify which bit needs correction, or if both, how much on each side. Thanks.

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bobbot32•

Well to start RNA degrades at a crazy fast rate due to RNAases scattered everywhere that we need more since a lot can get degraded before getting translated. The delivery system of lipid droplets can help mitigate the effect but its not going to be perfevt protection. At that id imagine lipid nanodrops arent nearly as efficient at integrating the RNA inside of our cells. Viruses have machinery to inject rhe RNA, lipid droplets its a crap shoot hoping we can get them to merge with the membrane annd send the RNA across.

I have no idea how efficient the lipid droplets are at integrating the RNA or its actual level of protection but theyre very likely concerns.

a few other things to note: every cell in our body has a few hundred thousand mRNAs in them already so a 3:1 for the vaccine compared to the cells we have is nothing compared to the total mRNA we have. In fact they likely try to have a local surplus of the viral mRNA just to gurantee that they can outcompete other RNAs for access to ribosomes by strict numbers.

Add in that our body already has a few trillion viruses on and in our body already it doesnt feel like thaaat much more compared to viruses already present. Youd he surprised by how much of modern biology techniques involve brute force and playing the numbers game lol

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binaryiceOP•

These are all good points. Do you know if the phagocytes consume the cells that have spike proteins or if they just "eat" the spikes off the exterior and leave the cell alone? I thought any cell with a spike would basically get sacced, which is why I thought 3 mRNA per cell seemed dangerous unless they sink dozens per cell, or there is a huge loss of delivery rate like you're talking about.. know where to look into these details?

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SNova42•

Cells that display a lot of foreign proteins will receive ‘kill signal’ from immune cells, basically telling them to self-destruct in a controlled manner. Phagocytes would eat the leftover pieces of a dead cell. They don’t normally eat whole, living self-cells because a living cell is typically connected to other cells and structures in a tissue, it’s not easy to swallow something stuck to a much bigger structure.

But even the kill signal thing is a number game. Cells have countless surface proteins, if they’re displaying only a tiny number of foreign ones there’s little chance of that actually tipping off an immune cell.

And yes, there’s a huge loss of delivery rate, and uptake is mostly concentrated to where you receive the vaccine, clearly demonstrated by how you get a sore on that arm which can last a few days, but you don’t get sore all over. They wouldn’t sink just dozens per cell, it’d be much, much more.

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binaryiceOP•

First of all, thank you for the refinement on cell destruction process. and just a quality response all around.

Someone asked me specifically about the impact of the vaccine on ooctyes in reproductive age females, and if there is any "threat" to the reproductive health through permanent change to the eggs that wont manifest until someone attempts to get pregnant. Well I'm inferring their concern here in large part, but I think it's a safe assumption on my part from the other things they have said.

I calculated the number of discrete sequences to be administered, expecting hundreds of thousands or millions of sequences that would go out and affect about that many cells, and then I could say "look, you've got trillions of cells, there's no real chance that you're going to see a lot of this tiny dose getting all the way down into the ovaries and ruining your reproductive future, it's just statistically a non issue, because most of the action is at the vaccination site."

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SNova42•

Well, vaccines don’t leave any lasting changes on your body, except the immune response. mRNAs given into cells gets translated to proteins, and then are destroyed in a matter of days. The proteins themselves don’t survive much longer.

Infertility from vaccines is essentially unheard of, including in COVID-19 vaccines. The ovary and eggs are relatively unaffected by immune processes, the only time you’d worry about infertility is when you get severe infection/inflammation in the abdomen or pelvic cavity (where the ovaries are), and even then it’s more about inflammation causing scarring of the fallopian tubes, rather than anything to do with the eggs.

See this CDC article on vaccine for the pregnant. It also lists many studies on women who went on to get pregnant and have child. No risk were found.

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