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Star33hcs

Dr Jerome

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hk81

I'm entering my subscription to attend this online Questions&Answers session.

When applying for the participation, it's possible to enter the topic in which we are interested in getting an update, or a short question.

Please, if more of us are applying for that and asking about the work of Jerome on gene editing of the latent HSV infection, it's more likely that they will give us an update. Today is the last day in which you can register for that.

If we don't move as a community in these few occasions, how can we expect to be heard?

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Laguna
6 hours ago, hk81 said:

I'm entering my subscription to attend this online Questions&Answers session.

When applying for the participation, it's possible to enter the topic in which we are interested in getting an update, or a short question.

Please, if more of us are applying for that and asking about the work of Jerome on gene editing of the latent HSV infection, it's more likely that they will give us an update. Today is the last day in which you can register for that.

If we don't move as a community in these few occasions, how can we expect to be heard?

Thanks! I signed up to attend the virtual town hall and asked about gene editing updates for HSV and broad spectrum antiviral research.

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TCBH

I signed up too and asked about the gene-editing work for HSV.

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Notgivinguphope

I signed up and asked about the gene editing work for HSV as well. 

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hk81

Thanks. I'm in the call. So far they are talking about covid19 testing, clinical trials for cancer, protection of cancer patients for covid19.

We have posted a couple of questions on HSV research (related in a way to covid19 epidemic). The reason for having more people participating is that questions can be upvoted to increase visibility.

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Franky26

I'm on the call as well. I was very happy when he said they are still working on the cure and they are getting some amazing result. Looking forward for what to come next

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Notgivinguphope

I'm on the call as well. That was really great to hear!

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Star33hcs
28 minutes ago, hk81 said:

Agradeço a Franky26 e a não-ação, e aos demais participantes. Conseguimos uma pequena atualização.

Um breve resumo:

Os presentes disseram que receberam algumas perguntas por e-mail sobre o trabalho de Jerome no HSV . Então ele perguntou se ele era capaz de continuar com seu trabalho, apesar da emergência secreta.

Jerome ficou agradecido pelo interesse que temos em sua pesquisa. Então ele respondeu que, de fato, a emergência teve um grande impacto em muitas atividades, mas não devemos nos preocupar. Sua equipe é altamente dedicada e eles conseguiram continuar com testes em animais. O artigo sobre os resultados em animais foi submetido.

Are they testing in pigs?

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hk81

He did not mention anything about it. We tried to keep the questions related to the covid19 situation or they would have been off-track

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Star33hcs

Do you think in 10 years Will be a a cure?

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hk81

Well, I'm no magician and I cannot predict the future. I hope it as much as you do

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MikeHerp

This is generally good news. While low on specifics, it does easy my concern that Covid19 has completely disrupted their animal testing. Apparently it’s not the case. I think this reply is about as good as we could hope for under the circumstances. Thanks for sharing,

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JHenry
7 hours ago, Franky26 said:

I'm on the call as well. I was very happy when he said they are still working on the cure and they are getting some amazing result. Looking forward for what to come next

Did he elaborate at all regarding the “amazing results”?  Thank you, Henry. 

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hk81

No, he has been very generic. Referring to the article, he said that it shows how the therapy can get rid of an impressive amount of viral copies in animals.

But I suppose that since the call was not about his research on HSV, he has kept it short and he just replied if his activities have been affected by the covid

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Cas9

@JHenry

Dr. Jerome's two HSV presentations were in 2019 (Jan and Nov). I re-watched the one in November (this time in its entirety), and although it's mostly a reiteration of his January presentation, he mentioned a couple of new and encouraging updates.

The first is, and you probably already know this, he will start his work on guinea pigs. They represent a better model for humans as opposed to mice. Also, Dr. Jerome's mice experiments were for the TG (the ganglion associated with oral herpes) and the SCG (superior cervical ganglion). Ultimately, we are interested in the DRG (dorsal root ganglion), not the SCG. The reason he targeted the SCG, is because it's difficult to work with the DRG in mice. With guinea pigs, the DRG will be easier to work with. So he'll be experimenting on the DRG and TG.

Also, indirect evidence suggests (albeit limited) that the DRG will respond well to viral cleavage; i.e. more like the SCG where 90% elimination was achieved, as opposed to the TG, where 50% elimination was cleaved. But we'll see if it holds true when he starts his work on guinea pigs.

Recall that the results of his experiments in 2018 were the 90% and 50% elimination. And he presented that in the January 2019 presentation. He also discussed how they were planning on achieving better results. After all, we would like to achieve close to 100% elimination in both ganglion. So there's still some work to do.  Dr. Jerome feels that the problem is that we are not getting the gene editor to all the infected neurons. Essentially, we have a delivery optimization problem.

Delivery is achieved via AAVs. There are several AAV serotypes and they vary as to which neuron types they are good at infecting. Note that a specific ganglion (e.g. TG), is made up of more than one neuron type. So if a specific AAV (we'll call it AAV1), is good at infecting one type of neuron in the TG, but not good at infecting another type of neuron in the TG, then the gene editor will not be able to cleave all the virus from that ganglion.

To improve delivery, they need to find which AAVs infect the most neurons in a target ganglion. That means that they'll likely need multiple AAVs for the target ganglion. Based on experimentation, they determined three of their best AAVs for delivery. They then tried them individually, then in combinations of two AAVs, and finally they tried all three AAVs together. The three AAVs together, provided the best results.

The experiment with the three AAVs included gene editing for only one cut, not two. This was done for simplicity because they were more focused on seeing how well the AAVs would do. The result was fantastic. They achieved a 60% reduction of latent virus, even though it was with just one cut. Remember, the 50% achieved in the older experiments, used two viral cuts. So the latest experiment achieved approximately a 10% increase in latent viral removal, even though it used only one cut. The next experiment will be with two cuts. Dr. Jerome thinks it has a solid chance of achieving 90%+ in the TG with the three AAVs and the two cuts.
It will also be very interesting to see what happens in the DRG with the three AAVs and two cuts.

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JHenry

Cas9, Thank you so very much for your response.   My background is in communications vs. science, so it took a few reads through for me to get a firm grasp on the concept(s). Sounds great to me—full steam ahead!  

Haven’t “talked” with you for a while, hoping all is well and good in your world.  On a bright note, as of today—I can look forward to a haircut the week of 5/11, wonderful news!  Take care and be safe—thank you again for the great news and response.  Henry.

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dont quit!17
1 hour ago, Cas9 said:

@JHenry

Dr. Jerome's two HSV presentations were in 2019 (Jan and Nov). I re-watched the one in November (this time in its entirety), and although it's mostly a reiteration of his January presentation, he mentioned a couple of new and encouraging updates.

The first is, and you probably already know this, he will start his work on guinea pigs. They represent a better model for humans as opposed to mice. Also, Dr. Jerome's mice experiments were for the TG (the ganglion associated with oral herpes) and the SCG (superior cervical ganglion). Ultimately, we are interested in the DRG (dorsal root ganglion), not the SCG. The reason he targeted the SCG, is because it's difficult to work with the DRG in mice. With guinea pigs, the DRG will be easier to work with. So he'll be experimenting on the DRG and TG.

Also, indirect evidence suggests (albeit limited) that the DRG will respond well to viral cleavage; i.e. more like the SCG where 90% elimination was achieved, as opposed to the TG, where 50% elimination was cleaved. But we'll see if it holds true when he starts his work on guinea pigs.

Recall that the results of his experiments in 2018 were the 90% and 50% elimination. And he presented that in the January 2019 presentation. He also discussed how they were planning on achieving better results. After all, we would like to achieve close to 100% elimination in both ganglion. So there's still some work to do.  Dr. Jerome feels that the problem is that we are not getting the gene editor to all the infected neurons. Essentially, we have a delivery optimization problem.

Delivery is achieved via AAVs. There are several AAV serotypes and they vary as to which neuron types they are good at infecting. Note that a specific ganglion (e.g. TG), is made up of more than one neuron type. So if a specific AAV (we'll call it AAV1), is good at infecting one type of neuron in the TG, but not good at infecting another type of neuron in the TG, then the gene editor will not be able to cleave all the virus from that ganglion.

To improve delivery, they need to find which AAVs infect the most neurons in a target ganglion. That means that they'll likely need multiple AAVs for the target ganglion. Based on experimentation, they determined three of their best AAVs for delivery. They then tried them individually, then in combinations of two AAVs, and finally they tried all three AAVs together. The three AAVs together, provided the best results.

The experiment with the three AAVs included gene editing for only one cut, not two. This was done for simplicity because they were more focused on seeing how well the AAVs would do. The result was fantastic. They achieved a 60% reduction of latent virus, even though it was with just one cut. Remember, the 50% achieved in the older experiments, used two viral cuts. So the latest experiment achieved approximately a 10% increase in latent viral removal, even though it used only one cut. The next experiment will be with two cuts. Dr. Jerome thinks it has a solid chance of achieving 90%+ in the TG with the three AAVs and the two cuts.
It will also be very interesting to see what happens in the DRG with the three AAVs and two cuts.

Nice breakdown.

Hypothetically, I'm wondering if editing of 90%+ of both TG and DRG in guinea pigs would be enough to start with a human trial, or simply progress onto a primate trial?

A 90% cleave of latent virus in human neurons, may be the answer that we have been looking for: a functional cure! Hopefully good results occur in these guinea pig trials; one trial at a time. 

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Cas9
7 hours ago, dont quit!17 said:

Nice breakdown.

Hypothetically, I'm wondering if editing of 90%+ of both TG and DRG in guinea pigs would be enough to start with a human trial, or simply progress onto a primate trial?

A 90% cleave of latent virus in human neurons, may be the answer that we have been looking for: a functional cure! Hopefully good results occur in these guinea pig trials; one trial at a time. 

At the end of the second video, Dr. Jerome was asked about testing on primates. https://youtu.be/Tk5EO6RerCk?t=3326

Although guinea pigs are a good model, primates are much closer. Given that it's gene editing I would think the FDA would want to see experiments in primates, especially for safety issues.

A 90% success rate may represent the lower limit for a practical cure, but we really want to get close to 100% of course and Dr. Jerome has not come to a dead end since he can use better and multiple AAVs. Perhaps if his results end up at 95% for both TG and DRG in primates, and he runs out of short term ideas to improve it, and in fact those percentages make you lesion free and there's no shedding, then I would assume he would move forward at that point and be satisfied with the 95%.

I can't wait for the results in guinea pigs with the AAV optimization.

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Cas9
Posted (edited)
9 hours ago, JHenry said:

Cas9, Thank you so very much for your response.   My background is in communications vs. science, so it took a few reads through for me to get a firm grasp on the concept(s). Sounds great to me—full steam ahead!  

Haven’t “talked” with you for a while, hoping all is well and good in your world.  On a bright note, as of today—I can look forward to a haircut the week of 5/11, wonderful news!  Take care and be safe—thank you again for the great news and response.  Henry.

Yes, hardly any of us are scientists so we just read articles (often multiple times) and also learn from each other. My background was in software engineering.

I'm doing as well as can be expected. Almost everyone is now wearing masks at the supermarket. There's also a limit to how many people can be in an establishment like a supermarket or a home depot for example. You end up in a line outside the building and they let you in as others leave the building. Not as bad as I thought; seems to take only 5 - 10 minutes to get in. Anyway, I assume you are seeing the same in your state.

I needed a haircut before the shutdown and missed my chance, so you can imagine how unruly my hair is now. The governor of NH plans on opening soon but in phases. I live in the NH county on the Massachusetts border and we have the highest incidence of Covid19 in the state, so we'll likely be the last to open. If it turns out our county wont be opening for another few weeks, I'll consider going to a different barber in another county. I need a damn haircut!!! :)

P.S. Be safe Henry, us over 65 crowd are more susceptible.

Edited by Cas9

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hk81

Just to show a comparison of a CRISPR therapy moving toward clinical trials:

https://excisionbio.com/editing-siv-nonhuman-primates-crispr-cas9-viral-reservoirs/

excisionbio tested their crispr therapy for hiv in a short number of primates (those bastards gave hiv to humans).
Even if they are moving toward clinical trials, apparently they did not study the effects of crispr long term (not more than 6 months) and whether it can eradicate completely hiv. They only show that the method works (in the sense that it cuts the dna of hiv where they expected) and that the gene vectors moved in the body and collected in the organs that are known to be a large reservoir for hiv. They did not release the monkeys from ART to check if hiv was becoming detectable again. Nevertheless on their website they plan to bring the therapy in clinical trials soon.

So I assume that there is not a real minimum requirement for the therapy to reach clinical trials, as long as it has been proven to be safe. It all depends from the amount of money that researchers get from their sponsors.

And: yes, the analysis on primates (with limited combinations) might be needed.

If you thought of disguising yourself as a primate (like I did), know that they will get euthanized

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MikeHerp

One of our HSV Cure members posted the relevant part of the clip from the recent FHC townhall where Dr. Jerome confirms that they have managed to keep the HSV cure animal testing going despite the disruptions from the coronavisu.  That's good news.

 

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Star33hcs
7 hours ago, MikeHerp said:

One of our HSV Cure members posted the relevant part of the clip from the recent FHC townhall where Dr. Jerome confirms that they have managed to keep the HSV cure animal testing going despite the disruptions from the coronavisu.  That's good news.

 

Mike do you think that is a real cure for herpes ?

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