Mindblowing New Paper on Gene Drive Eradication Strategy

[vzhe]

Check this out: https://www.biorxiv.org/content/10.1101/717017v1

"We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses."

Full PDF https://www.biorxiv.org/content/biorxiv/early/2019/07/30/717017.full-text.pdf

[raka]

Can you give brief details on it? i am not quite sure what they were saying.

[LightafterDarkness]

Fascinating read- there has been talk of doing this for mosquitoes but did not think something could be applied to the virus world.

 

Gene drive here basically means you are pushing a certain set of genes throughout a population. Man has been doing that for centuries when you think about the food and animals that we cultivate- we pick certain types of fruits or animals for breeding to get to a set of desired tastes / traits (for example the apple is what it is today because we picked for a certain look over centuries, same with cows or dogs or cats etc.). In this case what this paper is doing is saying what if we could do the same with herpes? I.e., could we create some sort of sterilized herpes virus and then see over time if it crowds out the other virus strains. At least in a petri dish the answer now is yes we can. Thinking ahead what this means is what if (1) you could introduce this sterilized virus into your body, (2) have this sterilized virus come into contact with other herpes virus and (3) replace them (the mechanism to me is not clear on how this has been done) such that you have a functional cure- i.e., this really weak virus that just floats around, is permanently latent, and does not shed. Its interesting because basically you are gene editing the virus itself and then sending it into the human body instead of gene editing the human body.

 

Its a novel idea but remember (1) its only been done for HSV-5 and (2) only a petri dish so far. Still, pretty cool!

https://en.wikipedia.org/wiki/Gene_drive

[vzhe]

2 hours ago, LightafterDarkness said:

Fascinating read- there has been talk of doing this for mosquitoes but did not think something could be applied to the virus world.

 

Gene drive here basically means you are pushing a certain set of genes throughout a population. Man has been doing that for centuries when you think about the food and animals that we cultivate- we pick certain types of fruits or animals for breeding to get to a set of desired tastes / traits (for example the apple is what it is today because we picked for a certain look over centuries, same with cows or dogs or cats etc.). In this case what this paper is doing is saying what if we could do the same with herpes? I.e., could we create some sort of sterilized herpes virus and then see over time if it crowds out the other virus strains. At least in a petri dish the answer now is yes we can. Thinking ahead what this means is what if (1) you could introduce this sterilized virus into your body, (2) have this sterilized virus come into contact with other herpes virus and (3) replace them (the mechanism to me is not clear on how this has been done) such that you have a functional cure- i.e., this really weak virus that just floats around, is permanently latent, and does not shed. Its interesting because basically you are gene editing the virus itself and then sending it into the human body instead of gene editing the human body.

 

Its a novel idea but remember (1) its only been done for HSV-5 and (2) only a petri dish so far. Still, pretty cool!

https://en.wikipedia.org/wiki/Gene_drive

That’s accurate. And it perfectly targets the same cells wild type would infect (unlike current AAV meganucleases to edit it out), and can even be made self-limiting. Eg make an ICP0 defective virus (Halford strain) that carries a gene drive instead. Result: virus is extremely slow to replicate, except in cells where wild type produces ICP0. Functional cure done.

[Freefalling87]

Are you saying that if someone has the virus and is given this edited virus, it will replace the wild type virus? If that is the case, I don't know how that could be because it would just infect other neurons that currently do not have the virus in them while the original wild type will still stay. 

Is it that this being an edited strain that the body will produce different antibodies towards it to reduce the original wild type outbreaks? Isn't that the same as a live vaccine? 

[vzhe]

3 hours ago, Freefalling87 said:

Are you saying that if someone has the virus and is given this edited virus, it will replace the wild type virus? If that is the case, I don't know how that could be because it would just infect other neurons that currently do not have the virus in them while the original wild type will still stay. 

Is it that this being an edited strain that the body will produce different antibodies towards it to reduce the original wild type outbreaks? Isn't that the same as a live vaccine? 

That's what a gene drive is, yes. Superinfection of the same cells plus gene editing means we can replace the original population.

Edited August 2, 2019 by vzhe

[LightafterDarkness]

@Freefalling87 im simplifying here but basically the gene edited virus would crowd out the other "normal" herpes population. If the gene edited virus has already moved into cells then that means the "normal" ones cant enter them because they are "taken." As a result its way more difficult for the "normal" ones to replicate and thus they are exposed in the open which allows your body to get in and pick them off. Meanwhile the gene edited virus continue sitting in your neurons but its just hanging out doing nothing. It does not shed, it does not replicate, it just hangs out -> functional cure

 

Edit: I may have it wrong, see below

Edited August 6, 2019 by LightafterDarkness

[vzhe]

On 8/3/2019 at 1:35 PM, LightafterDarkness said:

@Freefalling87 im simplifying here but basically the gene edited virus would crowd out the other "normal" herpes population. If the gene edited virus has already moved into cells then that means the "normal" ones cant enter them because they are "taken." As a result its way more difficult for the "normal" ones to replicate and thus they are exposed in the open which allows your body to get in and pick them off. Meanwhile the gene edited virus continue sitting in your neurons but its just hanging out doing nothing. It does not shed, it does not replicate, it just hangs out -> functional cure

That's actually inaccurate. Superinfection (multiple different strains infecting the same cell) is a regular event. It's just that the gene drive strain lacks a protein that is needed for fast replication. The gene drive strain only replicates when there's wild type around. In addition to that, it contains code to edit the DNA of wild type to modify wild type so that it becomes the gene drive strain. So if there's gene drive strain around, and wild type around, the gene drive strain converts the wild type into gene drive, and then, because a key protein is now no longer being produced, stops replicating. Thus it's a self-limiting infection.

[LightafterDarkness]

@vzhe interesting- are you positing that the gene edited virus only starts (major) replication in the presence of the "normal" herpes virus and then somehow manipulates the dna of the "normal" virus? If yes, thats pretty wild and would love to read more if you have a link handy. In particular I would be interested to understand how the gene-edited virus is able to subvert the "normal" virus.

[vzhe]

https://www.biorxiv.org/content/biorxiv/early/2019/07/30/717017.full-text.pdf

[LightafterDarkness]

Many thanks for the share!