Reddit Thread on HIV with Discussion about CRISPR

[Evaluate]

Background: For those of you who don't know what reddit is, it's like a massive online forum but instead of having a general topic (like honeycomb is with herpes) it has a crazy amount of topics and boards called subreddits.  r/science is a respected subreddit whose moderators confirm the qualifications of many posters (i.e. people must send proof of degrees to moderators in order to receive a tag next to their name), which I think is cool.  They also have strict rules about content, which helps keep false claims from being posted as factual (which is really needed into today's society).

Anyway, someone posted yesterday about new research into HIV.  A discussion came up about CRISPR, which is a fairly new technology that has potential application for HIV or HSV and could cure the infection.  CRISPR was discussed in a previous thread you can find here.  My reason for posting this discussion is because it has some really interesting points about the new technology and, although it's mostly in the context of HIV, it certainly can be carried over to HSV.

https://www.reddit.com/r/science/comments/3ul2sh/scientists_have_found_that_two_proteins_called/

I've taken some of the interesting responses and put them into a quotation below.  There is much more discussion inside the link above.  Enjoy.

Quote

CRISPR, baby. I think the iceberg's tip is just barely peeking over the horizon with what we could do.

[–]twiddlingbits 10 points 19 hours ago 

ELI5 on CRISPR please, it sounds very interesting.

[–]SadnotGrad Student | Comparative Functional Genomics 14 points 18 hours ago 

We can now make a protein, or cause cells to make a protein, that targets a specific sequence of DNA and cuts it. We could do this before, actually, but the CRISPR system is much faster. This is because it's composed of two parts: the protein itself and a guide RNA that specifies the target.

The guide RNA is cheap and easy to make and the cutting protein never changes, so that can always be on hand. This means we can set up the system in about two weeks, about half the time of the next best system. As well, it's a hell of a lot cheaper.

Finally, it's also more versatile, accurate, and thorough in some ways than the next best technologies for targeting DNA.

[–]Helassaid 10 points 19 hours ago 

The CRISPR/Cas system is a kind of "acquired" immunity in prokayotes. CAS proteins see viral DNA and create a template called a "spacer" in the CRISPR array of the organism's chromosome. The spacers then get transcribed into multi protein units with processed RNAs specific to the pathogen. They then seek out any of the viral DNA and snip it out of the organism's chromosome.

Now, imagine being able to engineer your own spacers, and being able to snip out genes for any number of diseases, or adding in any number of genes to do certain things.

Theoretically, CRISPR could be refined to cut HIV out of CD4+ T-cells. Or even more valuable: hematopoietic stem cells could be given CRISPR genes to continually check for HIV DNA, and effectively build HIV-resistant immune systems for HIV sufferers.

[–]thisdude415Grad Student|Biomedical Engineering 1 point 13 hours ago 

CRISPR is a way to chop DNA at precise places. The idea is that you could chop the DNA where HIV hides. Unfortunately this is more an idea than a therapy as far as I know.

We'd likely have to package it inside a virus to deliver it, too. And it's quite risky, so I don't think it will be a viable HIV therapy any time soon, especially since HIV is extremely manageable with antiretroviral drugs now.

[–]Alame 6 points 20 hours ago 

Definitely one of the most exciting areas of genetics research at the moment. I anticipate we'll see a Nobel prize for CRIPSR/RISC research within the next decade.

 

[dont quit!]

Interesting link. I was reading some of the comments on there. Hopefully they work with little to no side effects.

[Evaluate]

It sounds like the technology is harder to use with HIV for some reason, the guy said it's risky compared to antivirals. Hopefully HSV doesn't pose the same challenges.

[Sanguine108]

HIV being a retrovirus, they'd be snipping into the host's nuclear DNA.   I could see the world of potential issues with that.

HSV, on the other hand, is extranuclear floating outside the nucleus.  So to deliver something to a cell to target DNA that's not within the nuclear-chromosomal DNA seems a lot "safer".

Gives me hope.  But I just want to see them actually test it in vivo.

[dont quit!]

12 minutes ago, Sanguine108 said:

HIV being a retrovirus, they'd be snipping into the host's nuclear DNA.   I could see the world of potential issues with that.

HSV, on the other hand, is extranuclear floating outside the nucleus.  So to deliver something to a cell to target DNA that's not within the nuclear-chromosomal DNA seems a lot "safer".

Gives me hope.  But I just want to see them actually test it in vivo.

One of those posts on Reddit said the same thing in regards to HIV; they would have to be super specific with the HIV clipping. They would have to develop that HIV gene-clipping specificity and then hope it didn't cause any adverse reactions.  I think it is possible but a ways off. They just have to keep researching concept.

The HSV would be way safer for the reasons you mentioned; I'm also very interested in what Cullen and Editas studies will show in vivo. Can't wait especially because I get that bad feeling that Genocea's vaccine is going to be as good as it gets.

Edited November 30, 2015 by dont quit!

[Evaluate]

1 hour ago, Sanguine108 said:

HIV being a retrovirus, they'd be snipping into the host's nuclear DNA.   I could see the world of potential issues with that.

HSV, on the other hand, is extranuclear floating outside the nucleus.  So to deliver something to a cell to target DNA that's not within the nuclear-chromosomal DNA seems a lot "safer".

Gives me hope.  But I just want to see them actually test it in vivo.

I've looked online and am trying to figure out what you mean.  A retrovirus, such as HIV replicates in a host cell while HSV, not-a-retrovirus, does it outside?

1 hour ago, dont quit! said:

One of those posts on Reddit said the same thing in regards to HIV; they would have to be super specific with the HIV clipping. They would have to develop that HIV gene-clipping specificity and then hope it didn't cause any adverse reactions.  I think it is possible but a ways off. They just have to keep researching concept.

The HSV would be way safer for the reasons you mentioned; I'm also very interested in what Cullen and Editas studies will show in vivo. Can't wait especially because I get that bad feeling that Genocea's vaccine is going to be as good as it gets.

It makes me glad that the HIV side is talking about CRISPR.  My hope is that with HIV investigating the technology, along with HSV, the chances for breakthroughs will be greater and faster.  The reality is that HIV will likely get more funding than HSV for researching this technique.

Edited November 30, 2015 by Evaluate

[Sanguine108]

Yeah, apparently HSV's DNA is extranuclear and hangs out in the cyoplasm of the cell.  It doesn't actually integrate itself into the host's DNA like HIV does when it reverse transcribes itself into the host.  So HSV DNA is floating around and it'll use the cellular machinery outside to do its thing.

I had a misunderstanding thinking that HSV was a retrovirus and someone on this board corrected me.  I looked it up just because I wanted to read it for myself and found references to support that.  But I can't seem to find it right now.

[Evaluate]

Ah ok, that makes sense.  I thought HSV was pretty crafty but from the sounds of it HIV is even more so.

With HSV laying dormant, would it not need to be fully activated for the CRISPR technology to work?  Would it not "pass over" HSV unless active?  I think I heard on the other thread that it would eventually deplete HSV from the system over time, but I'm just trying to get a picture in my head.

Edited November 30, 2015 by Evaluate

[dont quit!]

3 hours ago, Evaluate said:

Ah ok, that makes sense.  I thought HSV was pretty crafty but from the sounds of it HIV is even more so.

With HSV laying dormant, would it not need to be fully activated for the CRISPR technology to work?  Would it not "pass over" HSV unless active?  I think I heard on the other thread that it would eventually deplete HSV from the system over time, but I'm just trying to get a picture in my head.

The hard thing about HIV is that is mutates rapidly so that is where gene editing is going to be a challenge for it. It will need a few gene editing approaches to stop it in it's tracks. HSV is a more stable virus and extra-nuclear so this might be the approach we are all seeking (well hopefully).

The CRISPR CAS 9 would use a vector (AAV) to smuggle itself into the neurons where HSV lays dormant. They had size issues but since has been resolved. With HIV, I'm not sure if they know where that damn virus lays dormant.

[JustHanginginThere]

There is a survey running where we can join debate on Gene Editing and results will be aggregated and shared in the media.  Tell them that a cure for Herpes Simplex 1 and 2 should be priorities.

To contribute to the survey please go to: http://www.whatisbiotechnology.org/survey/index/670a773b/conv12 Results are to be published both online through WhatisBiotechnology.org and other media outlets.

 

Here is the article mentioning the survey:

http://theconversation.com/the-public-must-speak-up-about-gene-editing-beyond-embryo-modification-48623

 

 

 

 

 

Edited November 30, 2015 by JustHanginginThere

[Sillybrain2]

1 hour ago, JustHanginginThere said:

There is a survey running where we can join debate on Gene Editing and results will be aggregated and shared in the media.  Tell them that a cure for Herpes Simplex 1 and 2 should be priorities.

http://www.whatisbiotechnology.org/index.php/survey/submit/670a773b

Hey, the link didn't work. Came up with an error.

[JustHanginginThere]

Fixed now.

[Evaluate]

Interesting find on the survey.  I responded.

[Herbfresh]

They just cured a girls incurable cancer with gene editing. Was big news. Google it. It happened like two weeks ago. 

But I doubt it will ever be used to cure HSV in our lifetime, unfortunately. 

[JustHanginginThere]

6 hours ago, Herbfresh said:

They just cured a girls incurable cancer with gene editing. Was big news. Google it. It happened like two weeks ago. 

But I doubt it will ever be used to cure HSV in our lifetime, unfortunately. 

Yes, that was news weeks ago.  The new news is that Cullen and Bloom are close to curing HSV in a rabbit model using gene editing and Editas is sponsoring him.  They just recently discussed that they feel AAV8 to achieve a cure using CRISPR/CAS.  I would say this definitely will be possible in our lifetime unless you are 90 (then probably not).

http://sites.duke.edu/cullenlaboratory/current-research/herpes-research/update-on-hsv-research/

Edited December 2, 2015 by JustHanginginThere