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Comment by purpleblue | Hacker News Reader

I wonder how many prions will be accidentally created by this, or if it can even predict if a particular protein will have prion-like effects

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It would be essentially impossible to create a new prion disease by accident- generating random-ish new things with methods like this would pale in comparison to the massive number of weird random-ish things natural biology is already creating in the wild.

However, this category of technologies could potentially be used to develop new prion diseases on purpose. As well as to develop cures for prion diseases that disrupt the misfolding.

>As well as to develop cures for prion diseases that disrupt the misfolding.

That seems quite plausible actually. You'd need something that can target misfolded PrP and bind it up so it can't do anything and then hopefully your targeting protein leaves normal PrP alone. A bit like an antibody.

The problem, from what I understand as a dabbler in protein research, is that PrP binds into these large very very stable semi crystalline fibers, (I visualize them looking like thick extruded complicated pasta shapes, where the 2d crosssection is kinda the shape of the outline of a single PrP). It makes it really hard to learn about the structure, actually, because x-ray crystallography requires repeated crystalline structures, and these are more like 3d polymer threads that bunch up and make things hard to image (though there's some more modern imaging techniques that are making headway). It turns out that these are very very stable configurations unfortunately and have very few ways to attach anything, and that's the precise problem with building binders. Plus, even worse, it turns out PrP might even be biologically necessary for mammals and we don't want to usually get rid of it wholesale [https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-01...]

The context here is that prions are misfolded proteins that replicate by causing other proteins to change their configuration into the misfolded form of the prion. Diseases caused by prions include Mad Cow disease, Creutzfeldt-Jakob disease, and Chronic Wasting disease. All prion diseases are incurable and 100% fatal.

If the protein is a novel it does not matter, because it has no normal variants in the nature.

Couldn’t the underlying tech be applied to non-novel proteins by a bad actor?

Someone could fine-tune a model on pairs of existing proteins and their misfolded prions and then ask the system to come up with new prions for other proteins. ChatGPT found these 4 companies that will produce proteins for you just based on digital DNA that you send them:

- Genewiz (Azenta Life Sciences)

- Thermo Fisher Scientific (GeneArt)

- Tierra Biosciences

- NovoPro Labs

Whelp, time to move to a small island in the middle of the Pacific.

One of the few cases where Mars actually is a decent planet B.

Oh this would be 100x worse than the covid lab leak

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