This resembles the Chinese HIV CRISPR study because the deleted receptor was CCR5, an immune receptor. This was controversial because we don't know the long term effects of of deleting CCR5.
Viruses often use immune or other surface proteins as receptors presumably because they are important (can't be down-regulated too much).
For the pigs, it looks like they deleted just the SRCR5 ___domain of the CD163 protein. CD163 is used by macrophages to scavenge the hemoglobin-haptoglobin complex.
A 2017 article (of 6 pigs?) suggests that the engineered pigs are resistant to the virus "while maintaining biological function" although I don't see any experiments comparing hemoglobin-haptoglobin scavenging ability of engineered vs unedited pigs.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5322883
This 2024 study (of 40 pigs) found 'no significant difference' in a panel of health measures and meat quality, except that the engineered pigs had statistically significantly more greater backfat depth than the edited animals.
https://www.frontiersin.org/journals/genome-editing/articles...
Interestingly, the mean weight of live pigs is slightly higher for edited pigs but lower for dead pigs. Total fat slightly higher for the edited pigs. These numbers are not statistically significant (but only a small number of pigs were tested).
The pigs were assessed at approximately 205 days in age. Pigs can live up to 20 years. Would be good to test the long term effects and the effects over multiple generations.
This paragraph is striking:
> Under the conditions of these studies, neither homozygous nor heterozygous or null pigs inoculated with PRRSV showed the acute clinical signs typically observed in commercial pigs and had overall low depression and respiratory scores (1). This may be explained by the fact that these pigs were sourced from a high-health farm and managed with minimal stress, which differs from disease expression under commercial conditions.
Sounds like the genetic editing is not necessary as long as the farm conditions are good..
> Sounds like the genetic editing is not necessary as long as the farm conditions are good..
And remember if you document or report on bad farm conditions in many US states, you’ll go to jail for telling the truth while the people running the farm do not.
Parent poster may be referring to laws on the books that forbid the sale of videos depicting where animals are subject to harm or treated cruelly. I suspect that these laws were passed in response to animal snuff videos a few years ago, but the law could be used to prosecute an activist, I guess - although it might also demonstrate the point the activist was making in order for a prosecution to pass.
w/r/t the HIV thing - there are HIV immune populations in Scandinavia who have a natural mutation affecting CCR5, so there is at least some reason to believe it’s safe to edit or knock out.
It's dangerous to assume that everything in biology exists because it's useful in some way. Some things are just spandrels* that came along for the ride, vestigial, or otherwise neutral features. Not everything exists because it provides an evolutionary advantage.
If a receptor is used as an entry point by a common virus and disabling it prevents infection but evolution has kept it around (cells spend energy actively expressing it, not having it encoded in the genome) then you can assume that there is a function provided by the receptor.
Turns out, CD163 already has a known function.
A spandrel not only has to have obvious function but removing it has to not be detrimental. I'm questioning the bar that is being used to say that it's not detrimental.
Unless humanity was on the brink of starvation and this was the only known way to increase food production then no it's not dangerous to be cautious.
On the other hand, I think it's dangerous to assume that a protein only has one function
I don’t believe so. I looked into it a bit more, and it looks like homozygous variant carriers are more susceptible to other types of infection (West Nile is specifically cited), but I don’t see anything showing the variant causes issues with CCR5s other critical functions. I do think a knockout is probably a bad idea based on further reading, but modification seems like a promising path.
> The pigs were assessed at approximately 205 days in age. Pigs can live up to 20 years. Would be good to test the long term effects and the effects over multiple generations.
It would be good to test for those things if the concern was for the long-term health of the pigs. The concern is whether or not they produce safe meat. Somewhere between most and all of the pork I've eaten in my life came from pigs less than a year old.
I understand that. But maybe at 205 days you won't detect a change which would more easily detectable later. Maybe we don't know exactly what to look for, but if something breaks over the long term that would give a clue.
They also only looked at the health of one generation, along with the number of offsprings from that first generation. What happens after 10 generations? 100? Could there be cumulative epigenetic effects from deleting this gene?
Viruses often use immune or other surface proteins as receptors presumably because they are important (can't be down-regulated too much).
For the pigs, it looks like they deleted just the SRCR5 ___domain of the CD163 protein. CD163 is used by macrophages to scavenge the hemoglobin-haptoglobin complex.
A 2017 article (of 6 pigs?) suggests that the engineered pigs are resistant to the virus "while maintaining biological function" although I don't see any experiments comparing hemoglobin-haptoglobin scavenging ability of engineered vs unedited pigs. https://pmc.ncbi.nlm.nih.gov/articles/PMC5322883
This 2024 study (of 40 pigs) found 'no significant difference' in a panel of health measures and meat quality, except that the engineered pigs had statistically significantly more greater backfat depth than the edited animals. https://www.frontiersin.org/journals/genome-editing/articles...
Interestingly, the mean weight of live pigs is slightly higher for edited pigs but lower for dead pigs. Total fat slightly higher for the edited pigs. These numbers are not statistically significant (but only a small number of pigs were tested).
The pigs were assessed at approximately 205 days in age. Pigs can live up to 20 years. Would be good to test the long term effects and the effects over multiple generations.
This paragraph is striking:
> Under the conditions of these studies, neither homozygous nor heterozygous or null pigs inoculated with PRRSV showed the acute clinical signs typically observed in commercial pigs and had overall low depression and respiratory scores (1). This may be explained by the fact that these pigs were sourced from a high-health farm and managed with minimal stress, which differs from disease expression under commercial conditions.
Sounds like the genetic editing is not necessary as long as the farm conditions are good..