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MikeHerp

Comments on recent study results on latent HSV by Keith Jerome

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LetsDoSomething

Trump just approved a $750b military budget after lamenting about exorbitant expenditure. 

Imagine if $1b of that was put into research and grants to solve problems like Herpes and other STDs. 

But the Pentagon needs to spend $300k  on coffee mugs. Don’t forget guys. Oh and trump just stopped movement for HIV research related to embryonic cells. 

Let us not forget our government is wholly incompetent and couldn’t care less about these issues that many of us face. 

Money talks. Great write-up Mike. You should send this to their research team, it may help them connect some dots. You never know. 

 

Edited by LetsDoSomething

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Trace67
5 hours ago, LetsDoSomething said:

Trump just approved a $750b military budget after lamenting about exorbitant expenditure. 

Imagine if $1b of that was put into research and grants to solve problems like Herpes and other STDs. 

But the Pentagon needs to spend $300k  on coffee mugs. Don’t forget guys. Oh and trump just stopped movement for HIV research related to embryonic cells. 

Let us not forget our government is wholly incompetent and couldn’t care less about these issues that many of us face. 

Money talks. Great write-up Mike. You should send this to their research team, it may help them connect some dots. You never know. 

 

Lol... it's not Trump's job to cure your herpes.

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hsv2fighter
19 hours ago, MikeHerp said:

我只是在这里大声思考,但最近发布的研究结果非常令人鼓舞。希望随后可以通过研究论文或大量的文章进行跟进,以便我们可以阅读详细信息。但在一个坚果壳中,似乎Keith Jerome在Hutch中心的团队能够使用内切核酸酶编辑近20%至30%的潜伏性HSV,如果我理解他最近的研究正确的有限模糊。

我喜欢这个是以下内容:  

1.在大约2年的时间里,他们的实验室已经能够提高编辑效率,从潜伏病毒的2%-4%到近20%到30%,如果我理解他最近关于他的正确的模糊。因此,在2年的时间内,编辑效率提高了5到10倍。我不一定会推断这些数字,但重点是,这项技术似乎在相对较短的时间内得到了显着改善。这很有趣,因为即使是2-4%的编辑,也似乎有一些复制HSV  病毒的中断目前还不清楚Keith Jerome是否也在这次编辑时进行了复制研究。如果他这样做,我认为这种编辑水平会导致复制中出现切实可衡量的中断。

2.过去,已经注意到CRISPR Cas9不能编辑非分裂神经元中的潜伏病毒。但是给出的原因是,在这样的神经元中处于静止状态的HSV对于CRISPR来说是非常困难的在关于杰罗姆最近工作的模糊中,还注意到他对CRISPR Cas9的努力无法编辑潜在的HSV,这肯定反映了之前的理解(尽管说编辑“不到1%”,似乎表明也许有一些非常非常小的编辑)。这也与EDITAS最近使用CRISPR Cas9的兔角膜HSV研究一致 ,这表明Cas9无法达到潜伏的HSV(即使它使角膜症状明显减轻)。很明显,CRISPR Cas9不能接触潜伏的HSV

但我注意到Jerome推测CRISPR不能很好地编辑潜伏HSV的原因Cas9的大小太大不能进行太多优化即,它不一定与位置有关,而是与编辑器的大小有关。如果你一直关注我在这里和我的博客上的评论,你会知道我对ExcisionBio关于HSV的努力有点半空洞的看法简单地说,虽然他们的方法很有趣,理论上可以阻止HSV复制,我从他们以前的工作中了解到,他们的努力集中在这样一种观念上:他们用CRISPR编写我们的身体,这些CRISPR必须不断地编辑新复制的病毒而不能接触潜伏的病毒。即使考虑到CRISPR安全性的持续改进,FDA似乎很快就会批准基因编辑治疗,这种治疗很快就会以CRISPR为中心无限期地在我们的身体中进行无休止的连续DNA编辑。这是可以理解的。即使非常轻微的目标编辑,当累积数年和数十年时,可能会让我们生病或更糟。那是我的想法。但是,如果问题更多的是关于编辑的大小,正如杰罗姆所建议的那样,也许ExcisionBio的努力可能会走上正轨。一直关注他们工作的人都知道,他们的意图是使用CasY而不是Cas9用于HSV2(尽管ExcisionBio提供的信息似乎有点缺乏和粗略,他们的网站有很多不足之处)。CasY比Cas9,所以如果Jerome的评论是正确的,也许它可能有机会编辑潜在的HSV。  Cas9杰罗姆在他的实验中使用的,与新发现的Cas类型相比,现在看起来几乎像旧技术。这很有趣,因为Jerome确实注意到Cas9 在体外编辑  HSV 非常高(大约50%),即使它对潜伏的HSV几乎没有做到

所以这对我来说非常有趣。 

但有各种警告。据我所知,杰罗姆的最新研究尚未发表。目前尚不清楚人类相对于老鼠可能会出现什么绊脚石。一个重要的问题是,某些潜在的HSV的部分编辑是否会允许部分治愈,以及这是否会继续如此。可以通过主动复制HSV重新接种“治愈的”神经元病毒再次?基因编辑是否需要无限期地留在细胞中(在我看来,从安全角度来看,这将使治疗更加可疑)。在他以前的工作中,杰罗姆注意到核酸内切酶在细胞中持续存在很长一段时间,这让我很奇怪。从安全角度来看,如果它们在我们的身体中不存在并且在编辑潜伏病毒后消散,那么它似乎是最好的。   

所以一些重要的问题仍然存在。但这个东西很有意思。  

 

Dear Mike, Could you please provide the original report about Dr. Jerome?

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MikeHerp

Hi hsv2fighter.  

I don't have a copy of the original report.  I'm posting in response to the information presented in this thread.

 

 

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Trace67
9 hours ago, LetsDoSomething said:

Trace, i assume you're here because you have herpes.

So, help me understand... It's not the role of our government to understand and address diseases, which include herpes?

Yet people, like you, who have this disease and understand it's physiological and social implications, make silly comments like this.

We live in a tone deaf society about Herpes. A world of socially-imposed isolation.  Society loves to shun people that are different or diseased. This permeates to the top levels of our government and society.  It's understandable that people without Herpes lack empathy and are tone deaf to the physiological and emotional issues sufferers carry-- i was guilty of this myself. But people who knowingly carry this disease, like you, I hold to a higher standard.

The whole notion that it's "Trumps job to cure my Herpes" is preposterous because that's clearly an inflammatory jab. Regardless of your stance on politics, in a utopian, progressive society, resources would be allocated to solve human problems. Herpes is a human disease and thus a human problem, and a progressive and collectively intelligent society would be allocating resources to solve human problems.

Instead, millions carry this disease and thousands more get infected daily. And the government has largely turned it's back.

Not only is it not Trumps job but I am glad that he doesn't get involved. He has much better things to do. The man barely has time to play golf these days so no he doesn't need to worry about your herpes. The government does have a program set up to deal with infectious diseases as well as others, but you should know that already. Bitching about Trump or Hillary or any president will not get rid of your herpes. You should have listened to those government programs that told you to use condoms, but you probably didn’t so you have only yourself to blame for the next 50 years. Condoms may not be 100 percent, but most of you wouldn’t be on this site had you listened. Herpes shouldn’t be anywhere near the top program that research dollars are spent. Things like cancer and several other life-threatening diseases should receive most of the money but back to the point; there is a program for that with people that make decisions. Think really, really hard, and I think you might figure it out. You can do it, man. If it really makes you feel better to blame Trump then, by all means, go ahead, but it won't do you any good. Crying in a safe room probably wont help either but…

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Miss Horne
On 12/11/2018 at 6:54 AM, MikeHerp said:

I'm just thinking out loud here, but the recent study results which were posted, were quite encouraging.  This will hopefully be followed up with a research paper or extensive writeup so that we can read the details.  But in a nut shell, it appears that Keith Jerome's team at the Hutch Center, was able to edit almost 20 to 30% of latent HSV in mice using endonucleases, if I understood the limited blurb about his recent research correctly.

What I like about this is the following:  

1.  In the space of around 2 years, their lab has been able to improve editing efficiency, from 2%-4% to almost 20% to 30%  of latent virus, if I understood the recent blurb about his work correctly.  So editing efficiency has been improved by more than 5 to 10 times in the space of 2 years.  I wouldn't necessarily extrapolate those numbers going forward, but the point is that, this technology appears to have been significantly improved in a relatively short time.  That's intriguing, because even at 2-4% editing, there seemed to be a hint of disruption of replicating HSV virus.  It's unclear whether Keith Jerome did a replication study post editing this time as well.  If he did, I'd imagine that this level of editing would result in a tangible and measurable disruption in replication.

2.  In the past, it has been noted that CRISPR Cas9 has been unable to edit latent virus in non-dividing neurons.  But the reasons that were given, were that HSV in its quiescent state in such neurons is a lot harder to access for CRISPR.  In the blurb regarding Jerome's recent work, it was also noted that his effort with CRISPR Cas9 was unable to edit latent HSV, which certainly mirrored the previous understanding (though by saying that editing was "less than 1%", it seems to suggest that maybe there was some very very minor editing).  That's also consistent with EDITAS recent rabbit corneal HSV study using CRISPR Cas9, which showed that Cas9 couldn't reach the latent HSV (even if it produced significant reduction of symptoms on the cornea).  It's pretty clear that CRISPR Cas9, as is, can't touch latent HSV.

But I noticed that the reason why Jerome speculated that CRISPR couldn't edit latent HSV well, was that the size of Cas9 was too large to allow for much optimization.  I.e., it wasn't necessarily related to the location, but rather size of the editor.  If you have been following my comments on here and on my blog, you'll know that I've taken a bit of a glass half empty view of ExcisionBio's efforts regarding HSV.  Simply put, while their approach was intriguing and could theoretically stop HSV replication, I had understood from their previous work that their efforts were concentrated around the notion that, they'd seed our body with CRISPRs that would have to continuously edit newly replicating virus while being unable to touch latent virus.  Even considering the continuous improvements in CRISPR safety, it just seemed kind of far fetched that the FDA would approve a gene editing treatment any time soon that was centered around CRISPR making endless and continuous DNA edits in our bodies indefinitely.  That's understandable.  Even very minor off target edits, when piled up over years and decades, might presumably make us very sick or worse.  That was my thinking then.  But if the issue is more about the size of the editor, as suggested by Jerome, than maybe ExcisionBio's efforts might be on the right track after all.  As people who have been following their work know, their intent is to use CasY not Cas9 for HSV2 (though the info provided by ExcisionBio seems a bit scant and sketchy and their website leaves tons to be desired).  CasY is smaller than Cas9, so perhaps it could have a chance to edit latent HSV if Jerome's comment is correct.  Cas9 which Jerome used in his experiments, seems almost like old tech now, compared to the newly discovered Cas types.  That's intriguing because, Jerome did note that Cas9 editing of HSV in vitro, was very high (around 50%), even while it did next to nothing against latent HSV.

So that's all very interesting to me. 

But there are various caveats.  Jerome's latest research hasn't been published yet, as far as I know.  It's unclear what stumbling blocks might arise in humans relative to mice.  One important question is, whether partial editing of some latent HSV would allow for a partial cure, and whether this would remain so going forward.  Could the "cured" neurons, be reseeded by active replicating HSV virions again? Would the gene editors need to remain in the cells indefinitely (that, in my view, would make the treatment more questionable from a safety perspective). In his previous work, Jerome noted that the endonucleases persisted in the cells for a prolonged period, which makes me wonder. From the safety perspective, it seems it would be best, if they didn't persist in our bodies and dissipated after editing the latent virus.   

So some pretty major questions still remain.  But this stuff is interesting.  

 

I wish Keith Jerome and the lab would update their web page, it hasn’t been updated in a while. I emailed them a while ago but unfortunately had no response. 

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Cas9
13 minutes ago, Miss Horne said:

I wish Keith Jerome and the lab would update their web page, it hasn’t been updated in a while. I emailed them a while ago but unfortunately had no response. 

Yes, I also emailed them but no response. It's been about a week I think

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Cas9
7 minutes ago, Miss Horne said:

Keith seems like a really nice guy :smile:

He does. Maybe I'll sit in the parking lot and wait for him to come out of the building. "Hey Keith, can I talk to you for a few minutes?" :)

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Miss Horne

Not sure if this has already been mentioned before, could we donate to his lab? Hsv specifically? 

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Cas9
1 hour ago, Miss Horne said:

Not sure if this has already been mentioned before, could we donate to his lab? Hsv specifically? 

If they do accept donations, it's probably not going to be hsv specific. But check their website.

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Miss Horne
23 minutes ago, Cas9 said:

If they do accept donations, it's probably not going to be hsv specific. But check their website.

Not hsv specific but perhaps someone could email the lab and ask? I’m sure they wouldn’t turn down donations. I would email myself but I have emailed them a while ago asking about progress and I wouldn’t want to come across as being a nuisance :giggle:

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Cas9
1 hour ago, Miss Horne said:

Not hsv specific but perhaps someone could email the lab and ask? I’m sure they wouldn’t turn down donations. I would email myself but I have emailed them a while ago asking about progress and I wouldn’t want to come across as being a nuisance :giggle:

Here's where to go to make a donation:
https://secure.fredhutch.org/site/SPageServer?pagename=adf_agiv&experience=evergreen&s_src=WEB&s_subsrc=aeuio9

Towards the top of the page you'll see the heading:  Directed Fund Option

and a text field below it with a down arrow on the right. If you click the down arrow you'll see a drop down list of where you want your donation directed. You'll notice there is not a selection for HSV.

So maybe under the Dedication heading, you can click the In Honor of button. That will provide you with first and last name fields.
Just fill in Genital for first name and Herpes for last name. Nah, that wont work :)

Edited by Cas9

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Newone2

This is slightly off topic but has anyone wondered what would happen if we just killed the cluster of nerves the virus is hiding in? I know in some extreme cases of  trigeminal neuralgia they will sever the trigeminal nerve to stop the pain and it usually results in partial paralysis or loss of sensation in the patients face. Being that the virus hides in those nerves would it possibly kill the latent virus? Crazy thought I know, but I think I would rather deal with numbness for the rest of my life then herpes.

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Cas9
9 minutes ago, Newone2 said:

This is slightly off topic but has anyone wondered what would happen if we just killed the cluster of nerves the virus is hiding in? I know in some extreme cases of  trigeminal neuralgia they will sever the trigeminal nerve to stop the pain and it usually results in partial paralysis or loss of sensation in the patients face. Being that the virus hides in those nerves would it possibly kill the latent virus? Crazy thought I know, but I think I would rather deal with numbness for the rest of my life then herpes.

You'd probably be totally paralyzed or dead. Whenever you ask a question like this you should contemplate why something as simplistic as removing the nerve cells has never been medically proposed or performed. That alone should tell you that it's not a viable solution.

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Newone2
8 minutes ago, Cas9 said:

You'd probably be totally paralyzed or dead. Whenever you ask a question like this you should contemplate why something as simplistic as removing the nerve cells has never been medically proposed or performed. That alone should tell you that it's not a viable solution.

Yeah I figured as much. I was reading up on Trigeminal neuralgia and it got me thinking what effect severing the Trigeminal nerve would have on someone with oral hsv. I’m sure risking potental  paralysis just to attempt curing hsv isn’t a  viable option. I guess that’s the main reason it’s been such a difficult virus to figure out. 

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Miss Horne
1 hour ago, Cas9 said:

Here's where to go to make a donation:
https://secure.fredhutch.org/site/SPageServer?pagename=adf_agiv&experience=evergreen&s_src=WEB&s_subsrc=aeuio9

Towards the top of the page you'll see the heading:  Directed Fund Option

and a text field below it with a down arrow on the right. If you click the down arrow you'll see a drop down list of where you want your donation directed. You'll notice there is not a selection for HSV.

So maybe under the Dedication heading, you can click the In Honor of button. That will provide you with first and last name fields.
Just fill in Genital for first name and Herpes for last name. Nah, that wont work :)

I think someone should contact the lab and ask, it wouldn’t hurt!

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Cas9
2 minutes ago, Miss Horne said:

I think Keith Jerome is our man :muscle:

I don't think Keith's biceps are that big. But who knows what's under that lab coat.

By the way, there are plenty of contact phone numbers on their website. They wont know that you've emailed them before if you call them now.

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Miss Horne
3 minutes ago, Cas9 said:

I don't think Keith's biceps are that big. But who knows what's under that lab coat.

By the way, there are plenty of contact phone numbers on their website. They wont know that you've emailed them before if you call them now.

Indeed who knows what’s under his lab coat :)

I’m in the UK, the phone call would cost me 6 months wages! I was hoping someone in the US could contact the lab .............

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Miss Horne
On 12/12/2018 at 2:42 AM, MikeHerp said:

Hi hsv2fighter.  

I don't have a copy of the original report.  I'm posting in response to the information presented in this thread.

 

 

Where did Tib Tola get this information from I wonder??

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Cas9
18 minutes ago, Miss Horne said:

Indeed who knows what’s under his lab coat :)

Well, I wasn't thinking about that part of his anatomy; LOL

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Miss Horne

Is Tib Tola an inside man perhaps??

10 minutes ago, Cas9 said:

Well, I wasn't thinking about that part of his anatomy; LOL

:joy:

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