Intranasal mRNA Vaccines?

post by J Bostock (Jemist) · 2025-01-01T23:46:40.524Z · LW · GW · 2 comments

Contents

  The Non-mRNA Components
  The mRNA
    Do not break these laws! This is not an "I refuse to say one way or another." situation here. Do not break national or international biohazard laws. They are there for a reason. Do not.
  Process
None
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This is not advice. Do not actually make this, and especially do not make this and then publicly say "I snorted mRNA because Jonathan said it was a good idea". Because I'm not saying it's a good idea.

Everyone remembers johnswentworth making RaDVac [LW · GW] almost four years ago now. RaDVac was designed to be, well, rapidly deployed, so it uses short peptides, rather than longer peptides or inactivated virus, which are what normal vaccines use.

 Since then, we've seen the introduction of mRNA vaccines, which can also be used intranasally! So would it be possible to produce something like this at home?

The Non-mRNA Components

mRNA vaccines consist of various. The first is the mRNA itself, the other components are a bunch of lipids (read: fatty molecules) which form into tiny particles rather unimaginatively called lipid nanoparticles (LNPs). These consist of a bunch of lipids surrounding the mRNA. Their job is to stick to cells, and then kind of merge with the cell's membrane (like two bubbles popping together into one big bubble) and release the mRNA into the cell. This works because the LNPs are cationic (positively charged) and cell membranes tend to be negatively charged.

There are sometimes other steps wherein the LNPs are actively taken up, transferred to an internal compartment, and then break out of that compartment.

So my first guess was to just buy something called Lipofectamine:

In this hypothetical case, we'd ignore steps 1 and 7, and replace step 6 with "huff it".

(Side note: "70-90% confluent" just means that the slides are 70-90% covered in cells, it has nothing to do with any property of the cells themselves, which is why we won't worry about it.)

The question is, would this work? Lipofectamine is probably similar to the lipid composition of the LNPs from this paper but not the same. I spoke to a friend whose job is getting nucleic acids into lung cells (lung cells and nasal cells are relatively similar) and (paraphrased) she said  "Don't DIY an mRNA vaccine" but then she said "Uptake rates for [those kinds of cells] are usually low ... but mRNA is easier to get into cells than what I work with".

So it's unclear whether lipofectamine as bought would work. There are lots of different lipofectamine formulations, but I can't at a glance tell which one would be best. Depending on the amount of this you want, it could be from $100 to $1000.

The mRNA

Our biggest obstacle here would likely be The Law. Ordering nucleic acid sequences for pathogens can be pretty difficult, especially outside the US. Most companies who'll provide this stuff are US-based, and there are strict export controls. I've had a lot of trouble ordering DNA sequences for pathogens before, but don't know the difference between DNA and mRNA in this case.

Having looked it up, I can't find any direct evidence of regulations on ordering relevant mRNA. The rules for mRNA might be looser than those for DNA, and they might only apply to full protein sequences, or proteins which are themselves harmful. (Example: I have had difficulty ordering bacterial toxin sequences since these are harmful on their own. A receptor-binding-domain of a viral protein is not harmful on its own, so there might not be issues there). In general, these things are usually only found out when one tries to actually order the mRNA.

Do not break these laws! This is not an "I refuse to say one way or another." situation here. Do not break national or international biohazard laws. They are there for a reason. Do not.

mRNA might set you back several $100s. You'd need 100 mig per dose, which is the minimum order from this custom mRNA supplier. They don't provide costs up-front, you have to ask for a quote, and I've not done that, so prices are estimates.

Process

In the best hypothetical case, you might be able to just order the mRNA for the whole protein of interest, dissolve this in the buffer which comes with the lipofectamine, mix with the lipofectamine, dilute in water (or some other buffer) and put it up your nose. In the worst hypothetical case, you'd need to find some gene fragment which isn't a fragment of concern.

Depending on how precise you want to be, it's totally possible that you wouldn't need any fancy equipment, unlike for RaDVac. I think the lipofectamine kit comes in pre-measured volumes of lipofectamine and mixing buffer, and the mRNA probably comes as lyophilized (dried) powder. So you'd just dissolve the mRNA in 100% of your buffer, then add the lipofectamine, dilute it (at this point you're working in mL quantities, and +/- 10% isn't really going to make a difference if you're DIYing a vaccine, let's be honest) and transfer to some sort of metered nasal spray dispenser.

If this protocol works, it would be much easier than what RaDVac currently have.

Overall I'd estimate ~$1000 for a single dose, but there's probably a quite large economy-of-scale factor on the mRNA. Since that's most of the cost, if it comes down by a factor of 10 then we might be able to achieve ~$200/dose for medium-sized (dozens of people) batches.

Once again I would like to say that this is mere speculation, I currently have no plans to test this, and I do not advise making this yourself!

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