CRISPR requires

A) a cas9 nuclease

B) very specific guide RNA sequence

Neither of which are present in mRNA vaccines. People don't endogenously expressed cas9, and mRNA vaccine sequences are designed to be expressed, not to bind to cas9.

If you are arguing "can mRNA vaccine tech approaches be used to make cells instead do weird and unconventional things", then...yeah, they could. That's not particularly useful, though, and it's not what vaccination is intended to do.

Do mRNA vaccines provide a convenient shortcut to immunity against novel emerging epitopes? Well, yeah, and this IS what they're intended to do.

So...use them for that.

Dear fellow, in what ways do you think that mRNA may interfere with endogenous gene expression ? I would appreciate a rather academic and not dogmatic way of thinking.

It just seems like a weirdly open-ended question, yet with the implication that there is some specific answer you are seeking.

There are a host of ways mRNA could interfere with gene expression: I mean, if you stuck in the mRNA for ricin, for example, you could "interfere with endogenous expression" by literally killing the cell. If you stuck in mRNA for a transcription factor, you could elicit expression of whatever gene products that TF influences. This isn't new science, and isn't particularly relevant to mRNA vaccines, which are by their very nature, not intended to do any of these things. I also don't really see how it has anything to do with CRISPR.

If you are proposing to use mRNA vaccine approaches to deliver mRNA for cas9 along with guide sequence, then...yeah, you could do that probably? It seems inefficient, and you might have issues with stochiometry, and it would certainly be more transient than a DNA vector approach.

One might question why it would be desirable to elicit genomic editing in a few cells directly adjacent to an injection site, and why you would take the mRNA approach when a DNA approach would be more effective.

Could you maybe be a little more specific about what it is you're looking for, here?

Dear fellow, I am very keen on molecular medicine you can look at my publications, however we are at unchartered waters. We have to admit that. Also please comment on the following paper I attach. How many bioethical rules should we bend ? As a medical doctor I can say that human is not equal to a laboratory rat.

Alright, a lot to unpick here.

This paper does not refer to an mRNA vaccine. Not even close. It's not necessarily even an mRNA delivery system (they discuss multiple ways of delivering the construct) and it's absolutely not a vaccine. It is a therapeutic, and a theoretical therapeutic at that.

I am tempted to start by saying "oh lord, can we please just stop trying to use CRISPR approaches for everything?", because that's sort of what this methodology suggests to me.

It's almost as if the authors of the original approach have gone "ooooh: CRISPR is hot right now, and so is covid19. Can we combine those, somehow? Instant paper!"

It's _neat_ and it's interesting, but "delivering a really quite large RNA-directed RNA nuclease along with an appropriate collection of guide RNAs, just to transiently tamp down on viral replication, maybe" is absolutely akin to using a petawatt laser to light up your garage. You can do it, and it would work, but better, cheaper, less ridiculous methods already exist.

Like, for example, the human immune system: that does an OK job. Combine that with dexamethasone to stop the overblown inflammatory response and you have yourself a pretty solid solution.

So there's that.

Also, it's Cas13, not Cas9, so it won't cut DNA, so risk of genomic edits are basically zero (especially since zero percent of the human genome will contain sars-cov2-like elements).

And it's been tested in cell culture only. Where it worked, a bit.

Nobody is proposing to immediately stick this into people (it isn't a vaccine, it's a therapeutic), and I doubt we could afford it anyway, even if we could decide on HOW to stick this into people. If we did, it might work, a bit, but the risk of off-target effects would be next to zero, because again it doesn't edit DNA.

The major take-home results would be "wow, that was expensive" and perhaps "gosh, we've now permanently seroconverted that person against CAS nucleases. I really hope we don't need to do any actual gene therapy in future".

CRISPR tech has the potential to be incredibly powerful, but the principal strengths, at least for now, are likely to lie in the sequence-directed genomic editing space, not the "hey let's just use this for anything and everything" space.