9 ms·

Mouse studies show gene therapy can cause big drop in latent herpes infections

157 points by johnny313 6y ago

doomlaser 6y ago
One could imagine this technique also working in latent reserves of coronavirus harbored by people who have become infected.
- 01100011 6y ago
  I'd really like to see what happens when we eliminate HERVs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187282/#:~:text=Human%20endogenous%20retroviruses%20(HERVs)%20represent,generations%20in%20a%20Mendelian%20manner https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187282/#:~:tex....) from our genome.
  - garmaine 6y ago
    It'd kill us. There are vital parts of our genome that come from such viruses. The placenta, for example, forms its host-compatible interface layer with the mother's uterus using a virus-derived protein. So it is believed that all live-birth mammals derive from an animal that accidentally incorporated viral DNA into its genome.
- garmaine 6y ago
  I don't think coronavirus hides itself in the same way? The long-lived herpes DNA folds itself up compactly inside the nerve cells, which is very unique capability specific to that type of virus. Attacking these dormant genes requires some specific molecular machinery to either keep these genes in their dormant state (current antiviral therapies), or to open and snip them up (TFA). I'm pretty sure coronavirus reservoirs are just regular virus sitting around in parts of the body the immune system doesn't reach. Different problem.
  - est31 6y ago
    Yeah Sars-Cov2 is a RNA virus. RNA is far more unstable in the long term. It needs replication to survive for longer times, even if it's only at low levels. Generally in most people, the immune system can clear out the virus itself sooner or later completely. Long term symptoms come from tissue damage. Only the small group of immuno compromised people form an exception (Think HIV, organ transplants, etc). Here, the immune system is not strong enough to get rid of the virus completely, thus it stays around for longer times. But they form a tiny subset, and therapies for them would look different.
    - garmaine 6y ago
      Very important to address these cases though, since it is believed that this is the source of the new variants that we are seeing now. Patients infected for months on end provide an ideal darwinian environment for the emergence of immune-escape variants.
      - est31 6y ago
        Indeed you are right, there have been reports of precisely this happening in such patients: https://www.latimes.com/science/story/2021-01-30/long-term-covid-19-patients-are-incubating-dangerous-new-coronavirus-strains https://www.latimes.com/science/story/2021-01-30/long-term-c... That's unrelated from my general point though. The virus is gone in almost all people reasonably quickly.
- newsbinator 6y ago
  I wonder if this would work for rabies.
  - hannob 6y ago
    Is there such a thing as dormant rabies? My impression was that most people die from rabies if they get it, so you really want to vaccinate people with any risk of getting rabies. And the vaccine is amazingly effective. (+ you can still give the vaccine once people are infected if you're fast.)
    - newsbinator 6y ago
      There've been documented cases of a person dying from rabies up to 8 years after infection.
RcouF1uZ4gsC 6y ago
.. In mice. It is unknown if it will work in humans. In addition, what are the long term consequences of causing multiple DNA cuts in nerve cells that the DNA repair mechanism cannot repair? There is still a very long, long way to go.
- deleted 6y ago
  [deleted]
- wnevets 6y ago
  >DNA cuts in nerve cells that the DNA repair mechanism cannot repair If I read the article correctly the "cuts" are made to the DNA of the virus, not the nerve cell itself. [1] [1] The hidden herpes viruses are disabled by an injection that tracks down infected nerve cells and induces them to make special gene-cutting enzymes, which work like a molecular scissors, to slash viral genes in specific places. Much of the team’s meticulous work of the past five years has involved finding better ways to target infected clusters of nerve cells and to thwart the virus’s ability to quickly repair the cuts to its genes.
  - mrtesthah 6y ago
    >If I read the article correctly the "cuts" are made to the DNA of the virus, not the nerve cell itself. [1] To further clarify, the herpes virus leaves DNA plasmids inside the cell nucleus; the virus' DNA is NOT incorporated into the cell's genome (like HIV) and the meganuclease delivered by the AAV cuts apart those plasmids -- not the cell's own DNA -- and in this version actually leaves behind its own plasmid that acts as a sentinel making more meganucleases to guard against future HSV infections in that cell. The researchers are investigating ways to remove those AAV plasmids when the job is done for added safety.
  - inglor_cz 6y ago
    Basically, you want the cuts to only happen where they should. Without so-called "off target" edits, undesirable changes elsewhere. We are becoming better with the molecular scissors, but 100 percent accuracy is AFAIK not there yet.
- 6y ago
technofiend 6y ago
That's fantastic! If it's successfully trialed in humans maybe they can go after HPV next. Yes, there's a vaccine but there are many more variants than even in the latest vaccine.
danielEM 6y ago
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917347/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917347/ Just reminded myself that above frome couple years back
- faitswulff 6y ago
  This seems like a safety study, what are the effects and efficacy of the treatment?
  - danielEM 6y ago
    No idea, just reminded myself similar "big news" dated couple of years back and the name of guy leading it ... Ian Frazer and that's how I found that paper
tijuco2 6y ago
What bothers me is that every single good news coming from science has the same old "but". >It will still take a long time before these experiments lead to the first human trials And we'll never hear from them again. You betcha!
- zionic 6y ago
  Look up when the electron was discovered, and how long electronics took to become a thing.
  - layoutIfNeeded 6y ago
    Actually, electronics were already in widespread use way before the discovery of the electron by Thomson in 1897... What you probably meant is the discovery of electricity.
- MattGaiser 6y ago
  Isn't this just the reality of science? A lot of things seem promising and then turn out to be duds?
- enriquto 6y ago
  Would you prefer that only 100% finished and completed science is communicated to you? It's nice to see the evolution of knowledge; and since it is a long process, most of the reports will be about incomplete stuff. Regarding such a common virus like herpes, I'm sure you'll hear from it very soon again!
  - symlinkk 6y ago
    Actually, yeah I would prefer that, instead of constantly hearing about things that never come to fruition and eventually tuning them out. It’s like the boy who cried wolf
    - whatshisface 6y ago
      Well, that's easy, just quit reading science news articles and watch for new items on shelves, or in commercials.
th0ma5 6y ago
I remember a study suggesting the Chickenpox vaccine suppresses outbreaks of HSV1 and HSV2 https://www.dovepress.com/efficacy-of-the-anti-vzv-anti-hsv3-vaccine-in-hsv1-and-hsv2-recurrent--a10554 https://www.dovepress.com/efficacy-of-the-anti-vzv-anti-hsv3...
- pmiller2 6y ago
  Well, that makes a lot of sense, because the chicken pox virus is in the herpesvirus family.
- 01100011 6y ago
  I wonder if that's why I've never had HSV1 despite my wife having had several outbreaks while we've been together. We aren't careful during outbreaks because I figure I'm going to get it sooner or later and we can't go weeks without kissing, but I've still never had an outbreak.
  - deleted 6y ago
    [deleted]
  - teraku 6y ago
    Some people never get outbreaks, but carry the virus regardless. So by not distancing you might prolong an outbreak for her.
  - throwaway189262 6y ago
    Over 50% of the population has HSV 1, many never show symptoms. I wouldn't worry about it , very likely you already had it for most of your life
known 6y ago
Can we get mRNA vaccine to Herpes
- mrtesthah 6y ago
  Inside the body, herpes viruses travel within continuous chains of neurons, so the immune system (antibodies, macrophages, etc.) can’t access herpes viral particles until they cross a single tiny gap between a sensory neuron and a skin cell. The narrowness of that opportunity for immune system action means that vaccines which work by stimulating antibody production (mRNA-based ones included) will have only limited effectiveness. Gene editing techniques like the one mentioned in the article will always be superior to traditional vaccines when it comes to herpes.
qchris 6y ago
> Nevertheless, she persisted. As a complete aside, I think this is a really interesting example of how a particular phrase has become part of the cultural vernacular. From the floor of the United States Congress, to t-shirts, to an article on herpes research. Pretty cool, imho.
jpxk 6y ago
My understanding is that herpes (both HSV1 and HSV2) are not actually bad but have enormous social stigma, which is the main problem. I wonder what can be done to address that, as an alternative strategy.
- ghevshoo 6y ago
  A significant part of the stigma comes from the fact that once caught, it’s for life. So curing it looks like the best way to also fix the social stigma.
- teraku 6y ago
  That is if you have weak symptoms. You can have HSV1 herpes which reactivates on certain triggers like stress or environmental changes and takes a hold of your whole skin, causing overall itchiness and leading to hospitalization for treatment. These people have to take takes suppressants their whole lives which causes stress on the liver and kidneys. A treatment of the root cause would be tremendous.
- henearkr 6y ago
  They are actually bad, with a risk of chronic latent infection that could extend to deeper in the brain, and also a strongly suspected link with the (still unknown) cause of Alzheimer's.
  - jpxk 6y ago
    You're right, I forgot about that connection.
- bipson 6y ago
  I have recurring cold sores next to my right eye. I had it in my eye as a kid as well. I could go blind any time I have it in my eye again. No joke - not exaggerating. I got it very early as a kid, and kids are bad at not touching their face, so I most certainly moved it from my nose to my eye at some point. I can also get it on my nose, in my nose, my lips, forehead. So far. My kid is now almost 3, we were very careful, but he got it a few months ago, had it 3 times in the last three weeks. It destroys our life. We have a 6 month old, it could be life threatening for the little one if they just touch. And even if only mild, explain to a 6 month old he should not scratch his patch off his face...
feralimal 6y ago
Hurrah for science! Hurrah for gene therapy! We are finally able to match God in creativity, and even improve the design! God/Nature was never that good anyway, we can give ourselves special powers now. Science ethics committees have discussed this, and they say its fine - we've had that discussion! Release the beast. Its not like my code is isn't perfect - I thrive when I barely have a handle on what a complicated function does, and can't even see it!
- Traubenfuchs 6y ago
  Taking charge of our evolution / genetics has always been humanities future and there is absolutely nothing wrong with eradicating disease and optimizing us however we see fit.
  - feralimal 6y ago
    Absolutely - we should do this everywhere! We should mandate in fact. Make sure that babies, the elderly, everyone have to get say, 'RNA' vaccines. Brilliant idea! What could go wrong? Nothing.
    - Traubenfuchs 6y ago
      Luddite.
    - mrtesthah 6y ago
      Do you think that mRNA vaccines work on a fundamentally different mechanism than any other vaccine developed in the last 70 years? They don’t. ‘What could go wrong?’ That’s an incredibly insulting perspective to take toward medical researchers who dedicate their entire careers to answering such questions.
      - call_me_dana 6y ago
        They actually do. But your definition of “fundamentally different” may be fundamentally different than mine.
jjxx1 6y ago
Hi! I have found this forum by google search. I see that you are talking about the research being conducted at Fred Hutch for HSV. If you still do no know, there is a Reddit Group that is in close contact with the researchers: https://www.reddit.com/r/HerpesCureResearch https://www.reddit.com/r/HerpesCureResearch I'm in the group as well, helping with moderation and awareness on this research. The group has started a fundraiser with Fred Hutch less than 2 years ago, in order to extend the study further to HSV2 and guinea pig testing, beside the research on HSV1 in a mouse model, supported by the NIH. The fundraiser has had a great success and it has collected all the needed funds for the study in Guinea Pigs through the donations from many sufferers and thanks to a large donation of 250k from one person. Because of this financial support that has been given, the researchers are in close contact with the reddit group that has supported their work and they communicate with them periodically during the year on the various milestones, sometimes to single members that are representative for the initiative, sometimes with an online meeting with questions and answers from all the participants. If you are interested in following more closely this research, you can join the group. The next milestones for this year are the communication between Fred Hutch and the FDA, to find agreements on starting clinical trials at the end 2023 - beginning 2024. After this, the reddit group will receive an update from these agreements and suggestions on how to support Fred Hutch further. At the end of summer the results of the study on Guinea Pigs will be presented to us. There are also opportunities of volunteering for the research group for the ones that live closer to their area. Know that this research is very active and it is aimed at reaching clinical trials and the market. Beside this, you will find many other informations on the website, like the similar research being conducted by ExcisionBio, in collaboration with Fred Hutch. And the clinical trial being done in China. Communications with Dr.Friedman on a therapeutic application of his vaccine and updates on clinical trials for herpes being conducted by other companies.

157 points by johnny313 6y ago

One could imagine this technique also working in latent reserves of coronavirus harbored by people who have become infected.

01100011 6y ago
I'd really like to see what happens when we eliminate HERVs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187282/#:~:text=Human%20endogenous%20retroviruses%20(HERVs)%20represent,generations%20in%20a%20Mendelian%20manner https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187282/#:~:tex....) from our genome.
- garmaine 6y ago
  It'd kill us. There are vital parts of our genome that come from such viruses. The placenta, for example, forms its host-compatible interface layer with the mother's uterus using a virus-derived protein. So it is believed that all live-birth mammals derive from an animal that accidentally incorporated viral DNA into its genome.
garmaine 6y ago
I don't think coronavirus hides itself in the same way? The long-lived herpes DNA folds itself up compactly inside the nerve cells, which is very unique capability specific to that type of virus. Attacking these dormant genes requires some specific molecular machinery to either keep these genes in their dormant state (current antiviral therapies), or to open and snip them up (TFA). I'm pretty sure coronavirus reservoirs are just regular virus sitting around in parts of the body the immune system doesn't reach. Different problem.
- est31 6y ago
  Yeah Sars-Cov2 is a RNA virus. RNA is far more unstable in the long term. It needs replication to survive for longer times, even if it's only at low levels. Generally in most people, the immune system can clear out the virus itself sooner or later completely. Long term symptoms come from tissue damage. Only the small group of immuno compromised people form an exception (Think HIV, organ transplants, etc). Here, the immune system is not strong enough to get rid of the virus completely, thus it stays around for longer times. But they form a tiny subset, and therapies for them would look different.
  - garmaine 6y ago
    Very important to address these cases though, since it is believed that this is the source of the new variants that we are seeing now. Patients infected for months on end provide an ideal darwinian environment for the emergence of immune-escape variants.
    - est31 6y ago
      Indeed you are right, there have been reports of precisely this happening in such patients: https://www.latimes.com/science/story/2021-01-30/long-term-covid-19-patients-are-incubating-dangerous-new-coronavirus-strains https://www.latimes.com/science/story/2021-01-30/long-term-c... That's unrelated from my general point though. The virus is gone in almost all people reasonably quickly.
newsbinator 6y ago
I wonder if this would work for rabies.
- hannob 6y ago
  Is there such a thing as dormant rabies? My impression was that most people die from rabies if they get it, so you really want to vaccinate people with any risk of getting rabies. And the vaccine is amazingly effective. (+ you can still give the vaccine once people are infected if you're fast.)
  - newsbinator 6y ago
    There've been documented cases of a person dying from rabies up to 8 years after infection.

RcouF1uZ4gsC 6y ago

.. In mice. It is unknown if it will work in humans. In addition, what are the long term consequences of causing multiple DNA cuts in nerve cells that the DNA repair mechanism cannot repair? There is still a very long, long way to go.

deleted 6y ago
[deleted]
wnevets 6y ago
>DNA cuts in nerve cells that the DNA repair mechanism cannot repair If I read the article correctly the "cuts" are made to the DNA of the virus, not the nerve cell itself. [1] [1] The hidden herpes viruses are disabled by an injection that tracks down infected nerve cells and induces them to make special gene-cutting enzymes, which work like a molecular scissors, to slash viral genes in specific places. Much of the team’s meticulous work of the past five years has involved finding better ways to target infected clusters of nerve cells and to thwart the virus’s ability to quickly repair the cuts to its genes.
- mrtesthah 6y ago
  >If I read the article correctly the "cuts" are made to the DNA of the virus, not the nerve cell itself. [1] To further clarify, the herpes virus leaves DNA plasmids inside the cell nucleus; the virus' DNA is NOT incorporated into the cell's genome (like HIV) and the meganuclease delivered by the AAV cuts apart those plasmids -- not the cell's own DNA -- and in this version actually leaves behind its own plasmid that acts as a sentinel making more meganucleases to guard against future HSV infections in that cell. The researchers are investigating ways to remove those AAV plasmids when the job is done for added safety.
- inglor_cz 6y ago
  Basically, you want the cuts to only happen where they should. Without so-called "off target" edits, undesirable changes elsewhere. We are becoming better with the molecular scissors, but 100 percent accuracy is AFAIK not there yet.
6y ago

technofiend 6y ago

That's fantastic! If it's successfully trialed in humans maybe they can go after HPV next. Yes, there's a vaccine but there are many more variants than even in the latest vaccine.

danielEM 6y ago

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917347/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917347/ Just reminded myself that above frome couple years back

faitswulff 6y ago
This seems like a safety study, what are the effects and efficacy of the treatment?
- danielEM 6y ago
  No idea, just reminded myself similar "big news" dated couple of years back and the name of guy leading it ... Ian Frazer and that's how I found that paper

tijuco2 6y ago

What bothers me is that every single good news coming from science has the same old "but". >It will still take a long time before these experiments lead to the first human trials And we'll never hear from them again. You betcha!

zionic 6y ago
Look up when the electron was discovered, and how long electronics took to become a thing.
- layoutIfNeeded 6y ago
  Actually, electronics were already in widespread use way before the discovery of the electron by Thomson in 1897... What you probably meant is the discovery of electricity.
MattGaiser 6y ago
Isn't this just the reality of science? A lot of things seem promising and then turn out to be duds?
enriquto 6y ago
Would you prefer that only 100% finished and completed science is communicated to you? It's nice to see the evolution of knowledge; and since it is a long process, most of the reports will be about incomplete stuff. Regarding such a common virus like herpes, I'm sure you'll hear from it very soon again!
- symlinkk 6y ago
  Actually, yeah I would prefer that, instead of constantly hearing about things that never come to fruition and eventually tuning them out. It’s like the boy who cried wolf
  - whatshisface 6y ago
    Well, that's easy, just quit reading science news articles and watch for new items on shelves, or in commercials.

th0ma5 6y ago

I remember a study suggesting the Chickenpox vaccine suppresses outbreaks of HSV1 and HSV2 https://www.dovepress.com/efficacy-of-the-anti-vzv-anti-hsv3-vaccine-in-hsv1-and-hsv2-recurrent--a10554 https://www.dovepress.com/efficacy-of-the-anti-vzv-anti-hsv3...

pmiller2 6y ago
Well, that makes a lot of sense, because the chicken pox virus is in the herpesvirus family.
01100011 6y ago
I wonder if that's why I've never had HSV1 despite my wife having had several outbreaks while we've been together. We aren't careful during outbreaks because I figure I'm going to get it sooner or later and we can't go weeks without kissing, but I've still never had an outbreak.
- deleted 6y ago
  [deleted]
- teraku 6y ago
  Some people never get outbreaks, but carry the virus regardless. So by not distancing you might prolong an outbreak for her.
- throwaway189262 6y ago
  Over 50% of the population has HSV 1, many never show symptoms. I wouldn't worry about it , very likely you already had it for most of your life

known 6y ago

Can we get mRNA vaccine to Herpes

mrtesthah 6y ago
Inside the body, herpes viruses travel within continuous chains of neurons, so the immune system (antibodies, macrophages, etc.) can’t access herpes viral particles until they cross a single tiny gap between a sensory neuron and a skin cell. The narrowness of that opportunity for immune system action means that vaccines which work by stimulating antibody production (mRNA-based ones included) will have only limited effectiveness. Gene editing techniques like the one mentioned in the article will always be superior to traditional vaccines when it comes to herpes.

qchris 6y ago

> Nevertheless, she persisted. As a complete aside, I think this is a really interesting example of how a particular phrase has become part of the cultural vernacular. From the floor of the United States Congress, to t-shirts, to an article on herpes research. Pretty cool, imho.

jpxk 6y ago

My understanding is that herpes (both HSV1 and HSV2) are not actually bad but have enormous social stigma, which is the main problem. I wonder what can be done to address that, as an alternative strategy.

ghevshoo 6y ago
A significant part of the stigma comes from the fact that once caught, it’s for life. So curing it looks like the best way to also fix the social stigma.
teraku 6y ago
That is if you have weak symptoms. You can have HSV1 herpes which reactivates on certain triggers like stress or environmental changes and takes a hold of your whole skin, causing overall itchiness and leading to hospitalization for treatment. These people have to take takes suppressants their whole lives which causes stress on the liver and kidneys. A treatment of the root cause would be tremendous.
henearkr 6y ago
They are actually bad, with a risk of chronic latent infection that could extend to deeper in the brain, and also a strongly suspected link with the (still unknown) cause of Alzheimer's.
- jpxk 6y ago
  You're right, I forgot about that connection.
bipson 6y ago
I have recurring cold sores next to my right eye. I had it in my eye as a kid as well. I could go blind any time I have it in my eye again. No joke - not exaggerating. I got it very early as a kid, and kids are bad at not touching their face, so I most certainly moved it from my nose to my eye at some point. I can also get it on my nose, in my nose, my lips, forehead. So far. My kid is now almost 3, we were very careful, but he got it a few months ago, had it 3 times in the last three weeks. It destroys our life. We have a 6 month old, it could be life threatening for the little one if they just touch. And even if only mild, explain to a 6 month old he should not scratch his patch off his face...

feralimal 6y ago

Hurrah for science! Hurrah for gene therapy! We are finally able to match God in creativity, and even improve the design! God/Nature was never that good anyway, we can give ourselves special powers now. Science ethics committees have discussed this, and they say its fine - we've had that discussion! Release the beast. Its not like my code is isn't perfect - I thrive when I barely have a handle on what a complicated function does, and can't even see it!

Traubenfuchs 6y ago
Taking charge of our evolution / genetics has always been humanities future and there is absolutely nothing wrong with eradicating disease and optimizing us however we see fit.
- feralimal 6y ago
  Absolutely - we should do this everywhere! We should mandate in fact. Make sure that babies, the elderly, everyone have to get say, 'RNA' vaccines. Brilliant idea! What could go wrong? Nothing.
  - Traubenfuchs 6y ago
    Luddite.
  - mrtesthah 6y ago
    Do you think that mRNA vaccines work on a fundamentally different mechanism than any other vaccine developed in the last 70 years? They don’t. ‘What could go wrong?’ That’s an incredibly insulting perspective to take toward medical researchers who dedicate their entire careers to answering such questions.
    - call_me_dana 6y ago
      They actually do. But your definition of “fundamentally different” may be fundamentally different than mine.

jjxx1 6y ago

Hi! I have found this forum by google search. I see that you are talking about the research being conducted at Fred Hutch for HSV. If you still do no know, there is a Reddit Group that is in close contact with the researchers: https://www.reddit.com/r/HerpesCureResearch https://www.reddit.com/r/HerpesCureResearch I'm in the group as well, helping with moderation and awareness on this research. The group has started a fundraiser with Fred Hutch less than 2 years ago, in order to extend the study further to HSV2 and guinea pig testing, beside the research on HSV1 in a mouse model, supported by the NIH. The fundraiser has had a great success and it has collected all the needed funds for the study in Guinea Pigs through the donations from many sufferers and thanks to a large donation of 250k from one person. Because of this financial support that has been given, the researchers are in close contact with the reddit group that has supported their work and they communicate with them periodically during the year on the various milestones, sometimes to single members that are representative for the initiative, sometimes with an online meeting with questions and answers from all the participants. If you are interested in following more closely this research, you can join the group. The next milestones for this year are the communication between Fred Hutch and the FDA, to find agreements on starting clinical trials at the end 2023 - beginning 2024. After this, the reddit group will receive an update from these agreements and suggestions on how to support Fred Hutch further. At the end of summer the results of the study on Guinea Pigs will be presented to us. There are also opportunities of volunteering for the research group for the ones that live closer to their area. Know that this research is very active and it is aimed at reaching clinical trials and the market. Beside this, you will find many other informations on the website, like the similar research being conducted by ExcisionBio, in collaboration with Fred Hutch. And the clinical trial being done in China. Communications with Dr.Friedman on a therapeutic application of his vaccine and updates on clinical trials for herpes being conducted by other companies.