5 ms·

The big problem is that the CRISPR would need to be delivered to 100% of infected cells. And as far as I know (I'm a biologist) nobody has a method that can ach

The big problem is that the CRISPR would need to be delivered to 100% of infected cells. And as far as I know (I'm a biologist) nobody has a method that can achieve a delivery rate of 100% in vivo.

cft 3y ago
That would be for a cure, but not for a recurrent therapy
- mlrtime 3y ago
  Do we even need a cure or therapy if we can essentially use this as a vaccine? Doesn't help people now, but may eliminate it as a threat for future generations.
  - huytersd 3y ago
    Well you can’t use it as a vaccine since there would be no hiv to preemptively excise.
    - 1letterunixname 3y ago
      What we need is a reliable CRISPR vaccine that confers the CCR5 SNP and essentially give it to everyone.
      - huytersd 3y ago
        Yeah, we don’t even need to get every cell at that point, just a sizable number of the CD4 cells that are relatively easily accessible. The HIV would destroy every CD4 that isn’t CCR5 by itself. The antibodies would clean up the rest of the virons. Theoretically that would work as a cure too if you could excise the hiv and insert the CCR5 widely enough.
- ac2u 3y ago
  Could that risk evolutionary pressure on whatever is left behind so that mutations emerge that are more aggressive?
  - SketchySeaBeast 3y ago
    If we assume that the treatment needs to reach the HIV cell to effect it, and that the danger is not 100% of the cells are reached, would it produce evolutionary pressure? The survivors aren't interacting with whatever got its buddies, right?
    - simcop2387 3y ago
      That itself is an evokutionary pressure. Whatever allowed them to get missed would get amplified by reproduction. Only if it's entirely utterly and only random chance and not something like the method doesn't target certain cells would it not be applying pressure
      - yau8edq12i 3y ago
        If you bomb a cow pasture with napalm, you aren't going to be left with napalm resistant cows. Just lucky ones. And luck isn't genetic.
        ac2u 3y ago
        You're viewing the cows in isolation here. Replace the cows with cancer cells with different mutations and it doesn't work anymore. There's research going with certain types of cancer where the doses of cancer-killing drugs isn't intended to eradicate all cancer cells, but to keep it at a level that's manageable with future treatments. The theory being that if you go too far, cells that are left with a "lucky" mutation can grow without competition, leaving the patient in an even-less treatable state down the line.
        yau8edq12i 3y ago
        ... Cancer cells? This is about HIV. What are you talking about?
m3kw9 3y ago
Does it need to be 100%? We have dormant viruses that are domant and would only activate when conditions are good, like colds, and we have ways to deal with it. It’s an analogy, for aids we would deal with it with meds and press it back there by turning it into a sort of nuisance like colds. The issue is cost and stigma of passing it. I for one still wouldn’t want aids to be as prevalent as the cold even if it’s super easy to deal with.
huytersd 3y ago
There are specific latent reservoirs the HIV hides in. It wouldn’t need to get every cell in the body, just have a favorable probability distribution to hit the reservoirs.
fasteo 3y ago
I thought the biggest problem was off-target editing (I'm not a biologist)
jjk166 3y ago
If you can get a reasonably high percentage then this might not be a problem. Include something in the crisper treatment that acts as a marker that protects the cells to which the treatment is successfully delivered. Then kill everything without the marker. I don't know what fraction of of your CD4 cells you need to maintain a healthy immune system, but I imagine even a double digit percentage reduction is probably tolerable, especially if the reduction is only temporary.
tslf 3y ago
In-vivo is hard but there are many talented teams working on this. In animals, a company called Verve has discovered how to make in vivo CRISPR work via nanoparticles to the liver which achieves >80% delivery at certain concentrations of nanos. Pretty fascinating

The big problem is that the CRISPR would need to be delivered to 100% of infected cells. And as far as I know (I'm a biologist) nobody has a method that can achieve a delivery rate of 100% in vivo.

cft 3y ago

That would be for a cure, but not for a recurrent therapy

mlrtime 3y ago
Do we even need a cure or therapy if we can essentially use this as a vaccine? Doesn't help people now, but may eliminate it as a threat for future generations.
- huytersd 3y ago
  Well you can’t use it as a vaccine since there would be no hiv to preemptively excise.
  - 1letterunixname 3y ago
    What we need is a reliable CRISPR vaccine that confers the CCR5 SNP and essentially give it to everyone.
    - huytersd 3y ago
      Yeah, we don’t even need to get every cell at that point, just a sizable number of the CD4 cells that are relatively easily accessible. The HIV would destroy every CD4 that isn’t CCR5 by itself. The antibodies would clean up the rest of the virons. Theoretically that would work as a cure too if you could excise the hiv and insert the CCR5 widely enough.
ac2u 3y ago
Could that risk evolutionary pressure on whatever is left behind so that mutations emerge that are more aggressive?
- SketchySeaBeast 3y ago
  If we assume that the treatment needs to reach the HIV cell to effect it, and that the danger is not 100% of the cells are reached, would it produce evolutionary pressure? The survivors aren't interacting with whatever got its buddies, right?
  - simcop2387 3y ago
    That itself is an evokutionary pressure. Whatever allowed them to get missed would get amplified by reproduction. Only if it's entirely utterly and only random chance and not something like the method doesn't target certain cells would it not be applying pressure
    - yau8edq12i 3y ago
      If you bomb a cow pasture with napalm, you aren't going to be left with napalm resistant cows. Just lucky ones. And luck isn't genetic.
      - ac2u 3y ago
        You're viewing the cows in isolation here. Replace the cows with cancer cells with different mutations and it doesn't work anymore. There's research going with certain types of cancer where the doses of cancer-killing drugs isn't intended to eradicate all cancer cells, but to keep it at a level that's manageable with future treatments. The theory being that if you go too far, cells that are left with a "lucky" mutation can grow without competition, leaving the patient in an even-less treatable state down the line.
        yau8edq12i 3y ago
        ... Cancer cells? This is about HIV. What are you talking about?

m3kw9 3y ago

Does it need to be 100%? We have dormant viruses that are domant and would only activate when conditions are good, like colds, and we have ways to deal with it. It’s an analogy, for aids we would deal with it with meds and press it back there by turning it into a sort of nuisance like colds. The issue is cost and stigma of passing it. I for one still wouldn’t want aids to be as prevalent as the cold even if it’s super easy to deal with.

huytersd 3y ago

There are specific latent reservoirs the HIV hides in. It wouldn’t need to get every cell in the body, just have a favorable probability distribution to hit the reservoirs.

fasteo 3y ago

I thought the biggest problem was off-target editing (I'm not a biologist)

jjk166 3y ago

If you can get a reasonably high percentage then this might not be a problem. Include something in the crisper treatment that acts as a marker that protects the cells to which the treatment is successfully delivered. Then kill everything without the marker. I don't know what fraction of of your CD4 cells you need to maintain a healthy immune system, but I imagine even a double digit percentage reduction is probably tolerable, especially if the reduction is only temporary.

tslf 3y ago

In-vivo is hard but there are many talented teams working on this. In animals, a company called Verve has discovered how to make in vivo CRISPR work via nanoparticles to the liver which achieves >80% delivery at certain concentrations of nanos. Pretty fascinating