4 ms·

CRISPR gene-editing treatment eliminates HIV-like virus from non-human primates

233 points by kibwen 3y ago

whimsicalism 3y ago
Wow this is super interesting! I’m just a layperson, but what’s interesting to me is that this seems distinct from past therapeutic uses of CRISPR that I am familiar with like CAR-T. In CAR-T, we use CRISPR to modify immune cells so they know how to attack the target (cancer). But in this approach, it seems more like we have created a new virus that uses CRISPR to directly edit and damage the SIV virus, which is nuts.
soligern 3y ago
If I’m not mistaken, EBT-101 human trials for HIV are under way as of last month. Hope this works out the same for humans.
- whimsicalism 3y ago
  https://www.cgtlive.com/view/excision-s-crispr-therapy-fast-tracked-for-hiv https://www.cgtlive.com/view/excision-s-crispr-therapy-fast-... "Approximately 9" participants seems surprisingly low. Although to be honest, if I were infected with HIV and on HAART, I think I would find it hard to justify to myself an experimental gene therapy when HAART is already pretty darn effective. But maybe I would... my understanding is the impact on life expectancy is still there once you get older. My guess is the constraint is more regulatory/clinical than lack of demand.
  - hadlock 3y ago
    9 seems adequate to get some kind of statistical significance from the results. Additionally if this somehow has a very high mortality rate, due to unseen consequences, 9 is a lower number than say, 300. In reality though, running medical trials is hugely expensive, the FDA requires all kinds of procedural documentation, as well as documentation of software code etc.
  - hiddencost 3y ago
    "to evaluate the safety, tolerability, and preliminary efficacy of EBT-101" The primary question is "will anyone die or have extreme negative side effects". They run the study small in this phase because it might kill or seriously harm the entire study population. Once they know that nothing extremely bad happened, they'll try on bigger populations.
    - whimsicalism 3y ago
      My understanding was this is actually a combined phase 1/2 trial not just phase 1
      - mlyle 3y ago
        That's (phase 2) the preliminary efficacy bit mentioned. But it's not really looking for a great, high quality signal: just some evidence that some indicators move in patients and not necessarily even statistical significance before moving to a phase 3 trial designed to measure benefit. They expect a big enough effect on the virus to be able to measure it in this tiny population.
mouse_ 3y ago
Awesome
bawolff 3y ago
Interesting. Is this supposed to be a cure or a treatment? It seems like to be a cure it would have to catch every instance of the virus in the body, which seems like it would be hard
est31 3y ago
This is a cool idea for a possible cure of HIV, and it's great to see researchers trying it out. But from what I heard, CRISPR is quite ineffective: when you want to do gene edits with it, you often do it to cell cultures, then keep only those cells where it actually worked. CRISPR does the cutting only, and you rely on cell repair mechanisms to mend the parts together again: they can be mended in any way. Also, the reservoir that makes HIV so tricky is in immune cells that are in a sleep state and only wake up every now and then: can the viral vector reach those? Also important quote from the paper: > The study was not designed to test the effect on the intact viral reservoir as EBT-001 was given when the viral reservoir was not stable and there was still active viral replication. Additionally, as animals were maintained on ART, we did not test the ability of EBT-001 to extend time to viral rebound or eliminate viral reactivation after an analytical treatment interruption.
- mycall 3y ago
  Is it possible that all viruses can wake in immune cells every now and then? I'm wondering how common this phenomenon is.
  - cyberax 3y ago
    Not many viruses can stay dormant. They need to be adapted for that. A classic example is the herpes virus, that has special proteins that regulate its expression. HIV is a retrovirus, it inserts itself into the hosts's genome, making dormancy easier.
- whimsicalism 3y ago
  > can the viral vector reach those? I think yes from the article? The whole point of this therapy is to eliminate latent HIV from dormant cells that traditional small molecule retroviral therapy can't access. > CRISPR does the cutting only, and you rely on cell repair mechanisms to mend the parts together again But in this case, all we need is the cutting right because we don't care if the HIV survives the interaction. Agreed on the quote
  - 3y ago
ck2 3y ago
Didn't they put someone in prison in China for doing this to babies? https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail https://www.science.org/content/article/chinese-scientist-wh...
- ben_w 3y ago
  Animal trials != human babies No suggestion of "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos" in this case, either. > The field of gene editing will carry the hashtag #CRISPRbabies in the mind of the public for a period longer than He's sentence, and that is an additional crime he committed but was not formally charged with," says Fyodor Urnov, a CRISPR researcher at University of California, Berkeley
- heavyset_go 3y ago
  No, not the same thing at all. The intent of that scientist was to purportedly edit genes that made some people susceptible to some HIV infections so that the virus won't be acquired. The intent in the OP is to remove virus genetics from infected cells' genomes with an existing HIV infection.
soVeryTired 3y ago
Is "eliminates" the right word here? My reading of the article abstract is that the treatment kills virus particles and in higher doses, the macaques showed increased white blood counts. But that's not to say that the monkeys are cured. Maybe "reduces viral load" might be a better phrasing?
- kibwen 3y ago
  It's quite possible that "eliminates" is not the right word, but I had a difficult time fitting all the relevant information into the title while remaining under HN's 80-character limit. The phrase that I would have preferred to use was "effectively removes".
Sparkyte 3y ago
Most news is source from places that are not reputable, with a lot of the publishings recently going under extreme scrutiny the best a person can do is look at any CRISPR advancement with optimism and wait patiently till all collective facts are in.Just in case anyone gets too excited.
- DiogenesKynikos 3y ago
  The source here is the journal Nature,[0] which is one of the two most prestigious scientific journals in the world (together with Science). That being said, Nature publishes the highest impact papers, which often turn out to be wrong (or overstated). Still, this isn't some random news source trying to report about science. 0. I realized after commenting here that the journal is Gene Therapy, which is part of the Nature Publishing Group, rather than Nature itself.
  - fsh 3y ago
    The article was published in the journal "Gene Therapy" which belongs to the Nature publishing group, but is far less prestigious than Nature.
    - DiogenesKynikos 3y ago
      Thanks, I just noticed that. I was deceived by the URL.
  - snoman 3y ago
    I know nothing about scientific publishing. Why is Nature still considered prestigious, if they often publish things that are wrong?
    - DiogenesKynikos 3y ago
      Because whenever someone has a really big result, they try to publish it in Nature or Science. By their very nature, big results are more likely to be wrong than small, incremental results. The main reason why Nature is prestigious is because getting published there means the scientific reviewers and editors think your result is really important.
pomatius 3y ago
P vs NP-like problem is solved for non-computer devices through advanced techniques

233 points by kibwen 3y ago

Wow this is super interesting! I’m just a layperson, but what’s interesting to me is that this seems distinct from past therapeutic uses of CRISPR that I am familiar with like CAR-T. In CAR-T, we use CRISPR to modify immune cells so they know how to attack the target (cancer). But in this approach, it seems more like we have created a new virus that uses CRISPR to directly edit and damage the SIV virus, which is nuts.

soligern 3y ago

If I’m not mistaken, EBT-101 human trials for HIV are under way as of last month. Hope this works out the same for humans.

whimsicalism 3y ago
https://www.cgtlive.com/view/excision-s-crispr-therapy-fast-tracked-for-hiv https://www.cgtlive.com/view/excision-s-crispr-therapy-fast-... "Approximately 9" participants seems surprisingly low. Although to be honest, if I were infected with HIV and on HAART, I think I would find it hard to justify to myself an experimental gene therapy when HAART is already pretty darn effective. But maybe I would... my understanding is the impact on life expectancy is still there once you get older. My guess is the constraint is more regulatory/clinical than lack of demand.
- hadlock 3y ago
  9 seems adequate to get some kind of statistical significance from the results. Additionally if this somehow has a very high mortality rate, due to unseen consequences, 9 is a lower number than say, 300. In reality though, running medical trials is hugely expensive, the FDA requires all kinds of procedural documentation, as well as documentation of software code etc.
- hiddencost 3y ago
  "to evaluate the safety, tolerability, and preliminary efficacy of EBT-101" The primary question is "will anyone die or have extreme negative side effects". They run the study small in this phase because it might kill or seriously harm the entire study population. Once they know that nothing extremely bad happened, they'll try on bigger populations.
  - whimsicalism 3y ago
    My understanding was this is actually a combined phase 1/2 trial not just phase 1
    - mlyle 3y ago
      That's (phase 2) the preliminary efficacy bit mentioned. But it's not really looking for a great, high quality signal: just some evidence that some indicators move in patients and not necessarily even statistical significance before moving to a phase 3 trial designed to measure benefit. They expect a big enough effect on the virus to be able to measure it in this tiny population.

mouse_ 3y ago

Awesome

bawolff 3y ago

Interesting. Is this supposed to be a cure or a treatment? It seems like to be a cure it would have to catch every instance of the virus in the body, which seems like it would be hard

est31 3y ago

This is a cool idea for a possible cure of HIV, and it's great to see researchers trying it out. But from what I heard, CRISPR is quite ineffective: when you want to do gene edits with it, you often do it to cell cultures, then keep only those cells where it actually worked. CRISPR does the cutting only, and you rely on cell repair mechanisms to mend the parts together again: they can be mended in any way. Also, the reservoir that makes HIV so tricky is in immune cells that are in a sleep state and only wake up every now and then: can the viral vector reach those? Also important quote from the paper: > The study was not designed to test the effect on the intact viral reservoir as EBT-001 was given when the viral reservoir was not stable and there was still active viral replication. Additionally, as animals were maintained on ART, we did not test the ability of EBT-001 to extend time to viral rebound or eliminate viral reactivation after an analytical treatment interruption.

mycall 3y ago
Is it possible that all viruses can wake in immune cells every now and then? I'm wondering how common this phenomenon is.
- cyberax 3y ago
  Not many viruses can stay dormant. They need to be adapted for that. A classic example is the herpes virus, that has special proteins that regulate its expression. HIV is a retrovirus, it inserts itself into the hosts's genome, making dormancy easier.
whimsicalism 3y ago
> can the viral vector reach those? I think yes from the article? The whole point of this therapy is to eliminate latent HIV from dormant cells that traditional small molecule retroviral therapy can't access. > CRISPR does the cutting only, and you rely on cell repair mechanisms to mend the parts together again But in this case, all we need is the cutting right because we don't care if the HIV survives the interaction. Agreed on the quote
- 3y ago

ck2 3y ago

Didn't they put someone in prison in China for doing this to babies? https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail https://www.science.org/content/article/chinese-scientist-wh...

ben_w 3y ago
Animal trials != human babies No suggestion of "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos" in this case, either. > The field of gene editing will carry the hashtag #CRISPRbabies in the mind of the public for a period longer than He's sentence, and that is an additional crime he committed but was not formally charged with," says Fyodor Urnov, a CRISPR researcher at University of California, Berkeley
heavyset_go 3y ago
No, not the same thing at all. The intent of that scientist was to purportedly edit genes that made some people susceptible to some HIV infections so that the virus won't be acquired. The intent in the OP is to remove virus genetics from infected cells' genomes with an existing HIV infection.

soVeryTired 3y ago

Is "eliminates" the right word here? My reading of the article abstract is that the treatment kills virus particles and in higher doses, the macaques showed increased white blood counts. But that's not to say that the monkeys are cured. Maybe "reduces viral load" might be a better phrasing?

kibwen 3y ago
It's quite possible that "eliminates" is not the right word, but I had a difficult time fitting all the relevant information into the title while remaining under HN's 80-character limit. The phrase that I would have preferred to use was "effectively removes".

Sparkyte 3y ago

Most news is source from places that are not reputable, with a lot of the publishings recently going under extreme scrutiny the best a person can do is look at any CRISPR advancement with optimism and wait patiently till all collective facts are in.Just in case anyone gets too excited.

DiogenesKynikos 3y ago
The source here is the journal Nature,[0] which is one of the two most prestigious scientific journals in the world (together with Science). That being said, Nature publishes the highest impact papers, which often turn out to be wrong (or overstated). Still, this isn't some random news source trying to report about science. 0. I realized after commenting here that the journal is Gene Therapy, which is part of the Nature Publishing Group, rather than Nature itself.
- fsh 3y ago
  The article was published in the journal "Gene Therapy" which belongs to the Nature publishing group, but is far less prestigious than Nature.
  - DiogenesKynikos 3y ago
    Thanks, I just noticed that. I was deceived by the URL.
- snoman 3y ago
  I know nothing about scientific publishing. Why is Nature still considered prestigious, if they often publish things that are wrong?
  - DiogenesKynikos 3y ago
    Because whenever someone has a really big result, they try to publish it in Nature or Science. By their very nature, big results are more likely to be wrong than small, incremental results. The main reason why Nature is prestigious is because getting published there means the scientific reviewers and editors think your result is really important.

pomatius 3y ago

P vs NP-like problem is solved for non-computer devices through advanced techniques