Cullen Update from Duke Website

[Fedfan]

Update on HSV Research

May, 2018

We are continuing our work on using CRISPR/Cas technology to cleave viral genomic DNA as a possible approach to the treatment of chronic diseases caused by human viruses, concentrating at present on Human Papilloma Virus 16 (HPV16), which causes malignant cervical, anal and head-and-neck cancers, as well as on HIV-1, the cause of AIDS. We currently have a paper in press that describes the use of CRISPR/Cas to treat HPV-16+ anal cancer explants in mice. In these animal experiments, we used Adeno Associated Virus (AAV) vectors as a tool to deliver Cas9 to the tumor cells in vivo, which resulted in a highly significant inhibitory effect on tumor growth. We are also about to submit a paper showing that we can not only stably protect T-cells in culture from HIV-1 infection using CRISPR/Cas but also cure the culture, that is remove all replication competent virus, and we hope to repeat these experiments in mice bearing a humanized immune system in the near future. We also have recently made an important breakthrough in  improving design and efficacy of AAV-based CRISPR/Cas delivery vectors that could have important implication for the use of CRISPR/Cas as an approach to the treatment of not only HIV-1 and HPV16 but also Hepatitis B virus (HBV) and Herpes Simplex Virus (HSV). Assuming this works as we expect, we then hope to reinvigorate our work on using CRISPR/Cas as a potential cure initially in animal models of HBV and HSV.

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Based on last couple of sentences, seems Cullen hasn't completely thrown in the towel on HSV just yet. Gotta love reference to "potential cure."  These guys are slow and steady and might just be the ones to get the job done.

Edited May 17, 2018 by Fedfan

[Evaluate]

Thanks for sharing!

I'm curious what breakthrough he speaks of.  I'm sure a paper will eventually come out on it.

[Taintedgirl]

We’ll see. I’m glad he got funding but maybe it’s just me but they shouldn’t throw the c word around until after the tests because there’s nothing worse than crushed hope. Stay safe and healthy everyone we’re all we’ve got on here. 

[Atrapasueños]

El no está trabajando en el vhs esta trabajando en otros virus pero si tiene algún tipo de éxito pasara al vhs, 

Una pregunta quién puede responderla se lo agradecería el virus del hsv al viajar por el axón y llegar a la neurona se replica dentro de ella o tiene que salir del axón y replicar en las células de la piel?

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He is not working on the vhs he is working on other viruses but if he has some kind of success he will go to vhs,

A question who can answer it would be appreciated by the hsv virus as it travels through the axon and reaches the neuron replicates within it or has to leave the axon and replicate in the skin cells?

[StayingUpbeat]

6 hours ago, Atrapasueños said:

El no está trabajando en el vhs esta trabajando en otros virus pero si tiene algún tipo de éxito pasara al vhs, 

Una pregunta quién puede responderla se lo agradecería el virus del hsv al viajar por el axón y llegar a la neurona se replica dentro de ella o tiene que salir del axón y replicar en las células de la piel?

________________________

He is not working on the vhs he is working on other viruses but if he has some kind of success he will go to vhs,

A question who can answer it would be appreciated by the hsv virus as it travels through the axon and reaches the neuron replicates within it or has to leave the axon and replicate in the skin cells?

The answer is yes to both.  In a practical sense an HSV infected neuron is simply a normal neuron that contains a snip-it of DNA encoding the directions to make more HSV.  For reasons that are not fully understood, the cellular machinery of an HSV infected neuron will occasionally read that HSV DNA snip-it and make copies of both the HSV DNA and envelopes to transport only the new DNA copies out of the cell.  The new copies of HSV DNA and the envelope to carry them out of the cell are referred to as a viron.  

Proteins on the envelope of the virons allow them to move down the branches (the axons) of the nerve to the skin's surface.  When the viron comes into contact with a living skin cell other proteins on it's coat bind with the cell's surface and translate it into the skin cell.  Once inside the cell the envelope dissolves leaving only the snip-it of HSV DNA again.  The cellular machinery inside the skin cell repeats the whole process of copying the HSV DNA and making the envelopes to pass the new DNA copies out of the cell.  The major difference in a skin cell is that this replication process is significantly more energetic.  So energetic that the skin cells fill with virons until they explode creating blisters and sores.

HSV's major trick is to have a non-energetic enough replication process in nerve cells to prevent killing them and so massively energetic a replication process in skin cells to ensure transmission to new hosts.  The copy of HSV DNA in the nerve cell that started this whole mess never leaves the cell.  It hangs out just beside the cell's natural DNA waiting for the cell's machinery to accidentally read it.

[MikeHerp]

This is a good update.  It sounds like Cullen is making some progress with CRISPR.  

[Atrapasueños]

Gracias por explicar ya que los artículos que veo la mayoría son en inglés y sólo dicen que el hsv viaja por los axones y réplica cuando sale de la neurona. 

Mi duda era si también se replicaban dentro de la neurona pero gracias por explicar, con razón es muy difícil curar el hsv 

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@StayingUpbeat

Thanks for explaining since the articles that I see most are in English and they only say that the hsv travels through the axons and replicates when it leaves the neuron.

My question was if they also replicated inside the neuron but thanks for explaining, rightly it is very difficult to cure the hsv