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.. 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.

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>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.

>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.

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.

I am baffled why you are being downvoted. While this research is very promising, it's also not hard for me to imagine a scenario where these targeted molecular "DNA scissors" do something unexpected. And while the risks of gene editing seems worth it for fatal or debilitating diseases, I don't think I'd want to be on a trial for this for a disease that is primarily an annoyance.

Again, I think the research and techniques are really cool, but your comment seems quite valid to me.

I think the social stigma attached to Herpes is more than "an annoyance".
We are still trying to figure out if some neurodegenerative diseases are caused by herpes viruses.

Having a vaccine is probably about the slowest way to figure that out, but if it turns out to be true then the problem is already solved.

There is also the correlation between HSV and dementia and Alzheimer’s.
Ok, well maybe this thread can be a tiny part of the solution to that stigma. First off herpes comes in two primary variants: HSV-1 and HSV-2. Most humans on Earth (between 60% and 95%) have HSV-1, and it's estimated that around 16% of humans have HSV-2. Herpes is extremely common. If you want references or more info, see the wikipedia page [0].

According to the article, the researchers are currently focused on HSV-1, and may work their way to HSV-2.

[0] https://en.m.wikipedia.org/wiki/Herpes_simplex

Supposedly they've stopped testing for herpes most of the time because of how likely it is someone has it, how unactionable the information is, and the stress it causes.
Anecdote: Doctors are certainly hesitant. I had to insist my doctor test me when I found out my then partner cheated on me.

At first glance, they're certainly reluctant to do so.

This kinda makes sense. A lot of people are asymptomatic carriers and there's not much you can do about it
> I don't think I'd want to be on a trial for this for a disease that is primarily an annoyance.

You can go blind, lose your sense of smell permanently, and get encephalitis from bad herpes outbreaks. It isn't just an inconvenience to those people.

And because herpes infects practically the entirety of the population, these problems are more common than you would expect.

And that's before we start chewing through all the viral data were going to get due to everybody actually paying attention to symptoms due to Covid. I suspect that the "viral hypothesis" people are going to have a field day for the next 10 years.

Thanks for your response, I wasn't really aware of the prevalence of herpes-related blindness and encephalitis.
his comment is trash and you supporting it makes you trash as well. please get up to date on how medical research is performed.
We've banned this account for repeatedly breaking the site guidelines.

If you don't want to be banned, you're welcome to email hn@ycombinator.com and give us reason to believe that you'll follow the rules in the future. They're here: https://news.ycombinator.com/newsguidelines.html.

you're also trash apparently.
in mice.. your comment is so helpful man. in mice is surprisingly useful and comments like yours make anything studied "in mice" out to be useless. please, get out of threads on the cutting edge of medical information, you aren't useful with your unwarranted cynicism and skepticism. please. LEAVE.
To rephrase the other (dead) "in mice" response with civility: ".. in mice" meme is more about studies where you have to read past the headline to know the study was on mice. In this case, "Mouse studies" opens the headline
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.
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!

Look up when the electron was discovered, and how long electronics took to become a thing.
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.

Isn't this just the reality of science? A lot of things seem promising and then turn out to be duds?
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!
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
Well, that's easy, just quit reading science news articles and watch for new items on shelves, or in commercials.
It's often the case. It's not always the case.

I remember the stories during the summer. "mRNA is promising, but there never was an mRNA vaccine that made it to the market. Nobody knows if it'll work."

Well, it does work. Amazingly so.

Yes, because in the political desire to solve the pandemic they lifted lots of regulation that make the approval of new medicines prohibitively expensive
And for the hundreds that have died from them already? I mean, not died from them. I mean died days to weeks after. They’re uhm, completely unrelated!

Would their families also agree that they work amazingly so?

that's not true. We will hear from them again. Read my reply to the previous comments
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...
Well, that makes a lot of sense, because the chicken pox virus is in the herpesvirus family.
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.
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Some people never get outbreaks, but carry the virus regardless. So by not distancing you might prolong an outbreak for her.
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

One could imagine this technique also working in latent reserves of coronavirus harbored by people who have become infected.
I'd really like to see what happens when we eliminate HERVs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187282/#:~:tex....) from our genome.
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.
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.

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.
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.
I wonder if this would work for rabies.
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.)

There've been documented cases of a person dying from rabies up to 8 years after infection.
Can we get mRNA vaccine to Herpes
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.
> 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.

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.
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.
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.

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.
You're right, I forgot about that connection.
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...

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!

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.
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.
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.

They actually do. But your definition of “fundamentally different” may be fundamentally different than mine.
Your immune system learns how to recognize a foreign antigen. The fact that your muscle cells' ribosomes are temporarily instructed to produce said antigenic proteins is immaterial to the fundamental mechanism of immunity. The mRNA stays in the cytoplasm and is not carried into the cell nucleus; it has no opportunity to affect the genome. The onus is on you here to present peer-reviewed evidence to the contrary.
No, mine is the accepted view and has been for years. Being that you are bringing a completely new outlook to the vaccination process, the onus is on you to provide evidence.

Anyone else who’s reading this, take note of what they did here. Say that mRNA gene therapy is the same fundamentally as traditional vaccines which is absolutely not the case. Then attempting to make the person espousing the traditional view provide evidence of the accepted fact. Liars like this need to be called out. They are NOT the same.

I was extremely clear in my wording and explanation. Your attempt to misconstrue my comment and intention, as well as your ad hominem attack, suggests you were never arguing in good faith from the start.
“Always” as in when statements like that starting appearing what, 50 years ago?

So... not always.

If we go into theology, then the nature is just a playground and the human body is just a complicated mechanism that a soul attaches to temporarily.
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 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.