This feels like being worried about sharks evolving machine guns.

A nightmare scenario for me is the creation of mRNA coding for a misfolded PRNP being weaponised.

I don't think you need to worry too much about that, honestly. as far as bioweapons go mRNA is pretty involved.. if you need to inject your victim, that's already way too complicated. bioweapons are much more oriented towards tainting water supplies or air.

I know a huge amount about the level of technical skill required to do something with mRNA. It’s involved today.

But in many ways it’s less technically involved than (re)creating the horse pox vaccine from scratch.

And in 20 years it could be as simple as something aerosolised (there are already research projects for nasal mRNA vaccines) we don’t know quite yet where this will all lead to - PRNP is small enough at 200-odd amino acids long that it can be easily encoded on mRNA and as a fucked up disease vector that’s surely worse than anything viral - a timebomb sitting in everyone’s bloodstreams waiting 5-50 years to go off

This probably isn't possible as the folding of PrP is not encoded in the mRNA of PRNP. The fold of PrP is a post-translational phenomenon, much like its glycosylation. This is true for many mammalian proteins, especially cell-surface proteins.

I’m aware of that. However the specific choice of amino acids can heavily influence the propensity to fold in a particular way. For example homozygotes for M129 have a much faster rate of vCJD development. Since Prion Diseases occur sporadically, the rate of mis folding can be increased and it probably wouldn’t be that difficult (even computationally) to determine how you can get it to misfold at a much higher rate.

I’m not sure what you mean by the fold being post translational, all folding is post translational, it’s literally the protein curling up into the lowest energy conformation as soon as it encounters the cellular environment, with assistance from HSPs if necessary. Unless you meant something else?