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CRISPR-Cas9 system-driven site-specific selection pressure on Herpes simplex virus genomesc

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JHenry

In short,  layman’s terms, please capsulize the end result and significance.  Thanks!

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MikeHerp

In a nutshell, the significance is this:

"As a consequence, it [CRISPR-Cas9] provides a feasible selection approach for identifying drug-resistant viral strains or screening attenuated vaccines, as well as being applicable for viral vector construction and reverse genetics research.

So, CRISPR can also be used to:

1. Identify drug-resistant viral strains of HSV1.

2. Screen and develop for attenuated vaccines.

3.  Create HSV viral vectors for genetic editing purposes.

 

Purposes 1 and 2 may have some relevance and could help in the future with developing treatments.  Here they are not talking about using CRISPR to inhibit replication of HSV, but rather to more quickly identify drug resistant HSV strains and helping to create attenuated HSV vaccine candidates.

It is saying that CRISPR may help with existing efforts to find solutions to HSV drug resistance and could make it easier to identify and develop attenuated HSV vaccines.  It's good news, but not news that will itself lead to a product. Rather, CRISPR may be used as a tool to help develop products in the future.  

 

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MikeHerp

This research is interesting for several reasons.  Good find Jimmy.  

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ManagingIllness

This is basically the conclusion of the paper:

The CRISPR-Cas9 system can recognize and cleave viral genomic DNA viruses in 
eukaryotic cells, but due to the presence of high-efficiency DNA repair systems in the cells, the viral DNA genome could be repaired after cleavage. Viral genomes in eukaryotic cells cannot be eliminated because of these repair mechanisms; however, their ability to replicate and produce progeny virus is inhibited. Although the ability of the CRISPR-Cas9 system to inhibit viral replication is weakened in the presence of DNA repair systems, it could still work well directly on nuclear DNA and even recognize single-nucleotide differences. This provides a more generalized tool as an alternative to antibiotic or reporter gene selection. Furthermore, the system targets DNA sequences but is not dependent on protein function. As a consequence, it provides a feasible selection approach for identifying drug-resistant viral strains or screening attenuated vaccines, as well as being applicable for viral vector construction and reverse genetics research.

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Taintedgirl
21 minutes ago, ManagingIllness said:

This is basically the conclusion of the paper:

The CRISPR-Cas9 system can recognize and cleave viral genomic DNA viruses in 
eukaryotic cells, but due to the presence of high-efficiency DNA repair systems in the cells, the viral DNA genome could be repaired after cleavage. Viral genomes in eukaryotic cells cannot be eliminated because of these repair mechanisms; however, their ability to replicate and produce progeny virus is inhibited. Although the ability of the CRISPR-Cas9 system to inhibit viral replication is weakened in the presence of DNA repair systems, it could still work well directly on nuclear DNA and even recognize single-nucleotide differences. This provides a more generalized tool as an alternative to antibiotic or reporter gene selection. Furthermore, the system targets DNA sequences but is not dependent on protein function. As a consequence, it provides a feasible selection approach for identifying drug-resistant viral strains or screening attenuated vaccines, as well as being applicable for viral vector construction and reverse genetics research.

They don’t want to hear you say it might not work as a cure. The system is great but enhancements need to be made to ensure delivery to the nerves and effective cleavage 

Edited by Taintedgirl

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Untouchable1
5 hours ago, About Blank said:

A little bit of sloppy science going on apparently. The off-target effects reported initially were exaggerated and researchers were not able to duplicate them. This article was also interesting. I was intrigued by the last few paragraphs in the article below pertaining to our genetic codes. Any progress is good progress.

https://gizmodo.com/after-a-few-hiccups-all-bets-are-on-crispr-again-1823521006

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Voyager2

@aboutblank and @untouchable1: Thank you! Your links say a paper has been RETRACTED, a paper that last year warned of CRISPR causing all kinds of dire "off target mutations." That paper was not connected to Editas, ExBio or the Jerome lab, all of which continue to work on gene editing. The labs will still have to prove safety, but we can be glad this particular warning was retracted. Let's hope safety AND efficacy will be confirmed quickly when the method is applied to HSV in humans. We can be optimistic again.

Edited by Voyager2

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valleynovascotia

How many years away is this?

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Voyager2
On 4/18/2018 at 7:00 PM, valleynovascotia said:

How many years away is this?

I think ExBio gives 2019 or 2020 on their website as the beginning of human trials, so we should be able to start following the testing fairly soon. That will give us something to be hopeful about. 

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MikeHerp

 I'd read ExBio's website info more as aspirational hopes rather than something that will definitely happen.  This is a privately held company that has been looking for funding.

It's an open question whether they will actually do the HSV trials.  We will see.  

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lookingforanswers18

Not Sure where everyone is from but 60 minutes is supposed to have news coverage about CRISPR this evening, Sunday 4/29/18. I am not saying their coverage will be about HSV, but it could be good to watch for more information on Crispr.

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Dope1
18 hours ago, lookingforanswers18 said:

Not Sure where everyone is from but 60 minutes is supposed to have news coverage about CRISPR this evening, Sunday 4/29/18. I am not saying their coverage will be about HSV, but it could be good to watch for more information on Crispr.

https://www.cbsnews.com/news/crispr-the-gene-editing-tool-revolutionizing-biomedical-research/

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Ajuda
On 4/21/2018 at 6:26 AM, Voyager2 said:

Eu acho que o ExBio dá 2019 ou 2020 em seu site como o início de testes em humanos, por isso devemos ser capazes de começar a seguir os testes em breve. Isso nos dará algo para ser esperançoso. 

in my opinion, we must surely have hope, even that is what keeps me going. But the fact of being published in the 2019/2020 excisionbio pipeline does not mean that they will follow this timeline, even because the clinical trials were initially for 2018 and has been postponed. We need to move if we want this treatment. Some things do not depend on us (science), other things (interest / pressure). Someone needs to go to Philadelphia and press. If not, do not expect anything in 2019/20.
What's more, the development of HSV treatment depends on the advancement of HIV treatment. Unfortunately.

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lookingforanswers18

I agree, but how do we go about applying pressure? I've noticed on previous threads making moves have been discussed, but nothing has been done. Not having funds & Stigma is hindering us.

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Alot of H hate

I'm starting to have real hope thanks to crispr. I just wish some how some way it could get even more media attention so it could be fast tracked to help out everyone! Like serious question when can this be available to everyone??

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Taintedgirl
9 hours ago, Alot of H hate said:

I'm starting to have real hope thanks to crispr. I just wish some how some way it could get even more media attention so it could be fast tracked to help out everyone! Like serious question when can this be available to everyone??

It is being used in some places as a diagnostic tool which I think will be the case for a while because it has failed to remove any of the virus from the nerve cells. It only successfully worked for EBV 

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