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This isn't my field, so apologies if I'm off-base, but this seems to make viruses do what they couldn't do previously, and moreover, target the brain. Wouldn't that qualify as GoF research? And if so, after millions dead and trillions lost, how prudent is it to conduct this kind of research?



They used AAV, which is a virus that doesn't cause disease.

https://en.wikipedia.org/wiki/Adeno-associated_virus

AAV9 can pass the blood-brain barrier (already), it says there.


"Gain-of-function" doesn't refer to adding literally any function to a virus, it refers to making it more virulent or transmissible -- that's why lots of people are so against it, because the cost-benefit ratio seems so obviously lopsided. Adding unrelated functions to viruses and using them as vectors isn't included in that, both in that it has lots more uses (some vaccines are made this way, for instance) and much lower downside risk (viruses used as vectors are often rendered unable to replicate, so the risk of them spreading at all is small).

> Wouldn't that qualify as GoF research? And if so, after millions dead and trillions lost, how prudent is it to conduct this kind of research?

While this isn't the main point, I feel like I should point out that (if I'm understanding you correctly) there seems to be something fundamentally wrong with your reasoning here. Whether or not it's a good idea to conduct this particular research is a matter of the facts of this particular case. How you categorize it doesn't change that. Learning what is or is not considered "gain of function" should have zero effect on your opinion here! Here's a good essay on this topic: https://www.lesswrong.com/posts/TyQSMmoJpRG3HBv5S/cleaning-u...


I should have asked GPT before wasting everyone's time. GPT4.5 says that while lethal and transmissible pathogens can be built with adenoviruses, nearly all research with them is done on replication-deficient viruses, and does not improve their transmissibility, pathogenicity, and does not expand the host range.


Why is it called "gain of function" if there's no gain of function?

> why lots of people are so against it

Hearing "GoF is NOT GoF" just makes me suspicious instinctively, that's all - no bad intention.


This is a nomenclature issue. But as a non-involved person, the key function of a virus is distribution/virulance. Gain of Function means increasing the effectiveness of the key function. So making a virus spread more, making an immune cell more effective against pathogens, making a retina cell more sensitive to light.

Gaining An Additional Function is not the same thing, although the confusion is understandable.


Understood, thanks for nicely explaining it instead of downvoting ;)


I assume, without reading the paper or being an expert, that they use the virus as a vector for their genetic payload, while also removing the reproduction instructions from it. Similar to the astrazeneca vaccines for covid19.


The virus is like that, but naturally occuring:

https://en.wikipedia.org/wiki/Helper_dependent_virus

"The most widely known dependovirus is adeno-associated virus (AAV)"

It's "replication-deficient", a "satellite virus": it requires help (from a different virus) to replicate.

(I don't know this stuff either, I'm just summarizing Wikipedia at you.)


Fun fact: The AAVR (AAV receptor) is itself a glycoprotein (carrying the precise type of glycosylation they are trying to repair with the “gene therapy”). Haven’t read up what replacement gene dose ended up being, but entirely within realms of possibility that this could influence which cells get corrected.


So that's, what, a protein on the outside of the cell that lets the virus in, like its own particular catflap? And you're saying this portal is made of mucus, and mucus is what they want to repair, and therefore ... nope, can't piece the conclusion together, sorry. "Could infuence", as in?


Catflap is a surprisingly apt analogy. In this case it is an endocytosis receptor, that selects cargo for uptake. Differs from virus to virus of course, but I could see changes in the sugars on these proteins altering behaviour. Mucus/mucins are basically proteins very heavily modified with sugars, so you have this common system that is adapted to do different things.


(endocytosis, into-cell-doing.)




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