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

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?