CRISPR Eliminates HIV In Live Animals (genengnews.com)

Researchers from the Lewis Katz School of Medicine at Temple University and the University of Pittsburgh show that HIV-1 infections can be eliminated from the genomes of living animals. Findings from the study have been published in the journal Molecular Therapy. Genetic Engineering and Biotechnology News reports: This is the first study to demonstrate that HIV-1 replication can be completely shut down and the virus eliminated from infected cells in animals with a powerful gene-editing technology known as CRISPR/Cas9. The new work builds on a previous proof-of-concept study that the team published in 2016, in which they used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals' bodies. They demonstrated that their strategy could delete the targeted fragments of HIV-1 from the genome in most tissues in the experimental animals. In this new study, the LKSOM team genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60% to 95% -- confirming their earlier findings. They then tested their system in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1. In the third animal model, a latent HIV-1 infection was recapitulated in humanized mice engrafted with human immune cells, including T cells, followed by HIV-1 infection. "These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection," Dr. Hu explained. Amazingly, after a single treatment with CRISPR/Cas9, viral fragments were successfully excised from latently infected human cells embedded in mouse tissues and organs.

Comments

Do you want a zombie apocalypse?

[LetterRip]

Because this is how you get a zombie apocalypse.

Re:Do you want a zombie apocalypse?

[Chrontius]

It's also how you get a cure for AIDS. Stop making zombie jokes, this could be the end of the epidemic.

Re:Do you want a zombie apocalypse?

[TiggerTheCat]

It's an experimental therapy being used in the lab. You won't know how much it might actually cost until they analyze what is involved in mass production. You can troll all you want but this news, this incredible wonderful news, will survive it.

Re:Do you want a zombie apocalypse?

[kilodelta]

Well that would be one epidemic down, a few others to go, or need I mention herpes.

Re:Do you want a zombie apocalypse?

[ceoyoyo]

CRISPR kits cost around $100-$1000. If you were to mass produce therapeutic CRISPR injections in batches of a million, they'd cost pennies per dose. The extra cost is recouping research, profit, costs associated with extra care for experimental patients, etc.

Re: Do you want a zombie apocalypse?

[walterhpdx]

Yeah, because gays are the only people affected by HIV/AIDS. Right.

Re:Do you want a zombie apocalypse?

[Salgak1]

The point being, it was the first. Bleeding-edge tech ALWAYS costs. The example of big-screen TVs is instructive. I'm in my mid-50s, and recall when any TV above a 26 inch tube was purely a rich man's toy. Price came down. Then flatscreen monitors, both TV and computer came out. Expensive and small. Now they're big and cheap, to the point you can pull a box with one off the shelf at your local Wally-world.

The same model applies to Medical Technologies. The only difference is, EVERYONE demands the bleeding edge (pardon the phrase) in medical technology. . .

Re:Do you want a zombie apocalypse?

[0123456]

In a few years, no-one's going to give a crap about whether these treatments are approved by some government, when they can download a file from the Internet that specifies the genetic changes and send it to their Home DNA Modification Kit.

Re: Do you want a zombie apocalypse?

[ArmoredDragon]

But AIDS is so 1980s. Cancer is what the cool kids have these days.

Oh wait, the word 'cool' is now retro too, having been replaced by the word "sick". So I guess the proper way to say it is "Cancer is what all the sick kids have these days."

Re:Do you want a zombie apocalypse?

[the gnat]

If I'm thinking of the same thing you are, the reason it is so expensive is that there are so few patients - like a few dozen. (It's not even clear to me why they pursued that in the first place, given that it seems like it would be impossible to even recoup their initial investment, much less make a profit.) There is a much larger pool of HIV patients (supposedly 1.2 million in the US alone), even if you just focus on rich nations, and they could still charge what sounds like an extortionate amount of money for it, because insurance companies and governments would love to not needing to keep paying for expensive HIV drugs every month. And whoever brings it to market could easily give it away to poor nations and still become spectacularly wealthy.

Re:Do you want a zombie apocalypse?

[ceoyoyo]

Funny. Except that you can buy CRISPR kits specifically designed for home experiments. Right now. For $100.

Re: Do you want a zombie apocalypse?

[Anonymous Coward]

HIV is a much bigger problem in 3rd world countries. And, contrary to your "belief", it is primarily a heterosexual disease outside the US.

Re:Do you want a zombie apocalypse?

[dintymoore]

Glad your parents didn't apply this philosophy to you while you were growing up? Or, maybe they did, and that's why you grew up to be an @$$hole.

Re:Do you want a zombie apocalypse?

[interkin3tic]

I don't think so.

HIV being a retrovirus puts its genome into the hosts genome. Basically it moves into a cell and settles in for the long haul, goes latent, then eventually sending out copies of itself at a leisurely pace. Other viruses like the cold come into cells and completely take over, pumping out copies of themselves in a mad dash, blowing up the cell in a matter of days, releasing more of the viruses. There's little time for the procedure here to take out the virus in such a situation: the cell is either uninfected or completely overrun by the time CRISPR would come along. With HIV, CRISpR can come along and take it out while it's hiding.

Moreover, HIV targets immune system cells roaming the blood. The researchers here injected the gene-editing vector (also a virus) into the blood where the vector also targeted the same cells. Other viruses don't do that. Rabies for example spreads inside nerves which are otherwise hard to target with viral vectors. HPV lives in the outer layers of the skin, safe from the immune system and any other easily injectable treatment. Cold viruses I believe infect the respiratory tract. None of these vector viruses are near 100% effective. You might have someone inhale a fog of the treatment, but at a minimum you'd need multiple treatments. No one is going to attempt to develop such a product for the cold due to liability problems alone.

Flabbergasted by the implications

[Chrontius]

This could actually move people off antiretroviarals, and into long-term remission.

Don't expect a silver bullet - AIDS will be cured like cancer, driven into remission, and only "cured" after we're confident that it won't show up again later on.

In spite of that? I expect it's going to be far cheaper than treating patients with long duration HAART cocktails, and treating the side effects of those drugs. Even if each patient's viral strains have to be sequenced, and a CRISPR cocktail picked based on the strains harbored, AIDS drugs are not cheap. This could be a turning point representing the beginning of the end of AIDS.

Re:Flabbergasted by the implications

[MayeulC]

Even if each patient's viral strains have to be sequenced, and a CRISPR cocktail picked based on the strains harbored, AIDS drugs are not cheap. This could be a turning point representing the beginning of the end of AIDS.

I agree. And this could also have the additional benefit of driving costs down for sequencing, and CRISPR-based therapies, which could in turn bring such a cure to more people, and enable the same to be done for other diseases.

Re:Flabbergasted by the implications

[Anonymous Cow Ward]

It'll almost certainly be cheaper long-term than HAART cocktails, but an effective HIV vaccine would do a lot more to end AIDS. Ideally, we'll get both a cure and a vaccine in the near future.

IIRC, this CRISPR/Cas system shouldn't require individualized patient sequencing. HIV does have highly conserved regions of its genome, and disrupting those is enough to render the proviral genome completely non-functional.

Re:Flabbergasted by the implications

[Anonymous Cow Ward]

No, OP is flabbergasted that it works well enough in an actual animal to eliminate integrated HIV copies. Plenty of things work well in isolated cells or tissues that fail to translate to animal models. Efficient delivery is usually a lot harder in animals than in cells.

Subtypes of HIV

[Gravis Zero]

HIV-1 is the most common and pathogenic strain of the virus.
HIV-2 has not been widely recognized outside of Africa.

HIV-2 has been found to be less pathogenic than HIV-1. The mechanism of HIV-2 is not clearly defined, nor the difference from HIV-1, however the transmission rate is much lower in HIV-2 than HIV-1.

source

Bill HIcks

[waspleg]

"I dunno how much AIDS scares y'all, but I got a theory: the day they come out with a cure for AIDS, a guaranteed one-shot cure, on that day there's gonna be fucking in the streets, man."

Re:Bill HIcks

[esperto]

His comment is tong in cheek, but one thing AIDS epidemic is "good" for, at least outside Africa, is to help keep in check other STDs. The AIDS scare helped a lot to make people use condoms and halted the spread of some common STDs that people took as not that bad (clamidia, herpes, etc.).

Not having this boogie man can actually make those other diseases spike.

Re:Bill HIcks

[gcmd]

And we are already seeing that spike as the spread of HIV has been greatly diminished with the use of HAART. Already Syphilis and Gonnorhea are spiking in incidence, and more worrisome, they are resistant to the drugs that we have used to treat them. Multidrug resistance is now a real problem with the older STDs!

CRISPR/Cas9's origin

[DrYak]

Not just that, but this sounds like an approach you could adapt to any virus.

Well, given how/why CRISPR/cas9 evolved in prokaryote in the first place.

Prokaryotes ended up with this systems because it helps them remove foreign DNA (phages, plasmids).
Curing HIV is about removing its foreign DNA from the infected white blood cells.

So CRISPR could be applied to curing viruses such as VIH.
Hey, what a surprise !

Yes, it could be used to eliminate tons of currently hard to cure viruses.

(Note: I'm not belittling the accomplishment of the researcher who developed this cure candidate.
There's surely a lot of work done to addapt to this use.

I'm just saying is that these kind of application is what bacteria evolved CRIPR for in the nature,
so it's not surprising that we could apply it for a similar task in eukaryote regarding viruses.

It's the "weirdly simple gene editor" use that is unexpected)

This is awesome

[Baron_Yam]

Gene editing, through every part of the organism reachable by the immune system, in a live mammal. HIV will ultimately be a mere footnote, because this technology is an early first step to editing your own genome as a consenting adult instead of fiddling around with the genes of a fertilized egg and hoping you haven't screwed over a future person's life in the process.

You won't be rebuilding large structures in the body with this, but there's still so much that can be done if you can alter genes in an adult. There are a lot of deleterious genetic conditions that can be corrected, and then you move on to upgrading.

Attention Baptist Preachers

[hyades1]

Remember when you guys were claiming AIDS was a sent by God to punish homosexuals?

Well, it looks like maybe God wasn't as pissed off with them as you thought. Oopsie!

Ob. link

[AnotherBlackHat]

Ob. link to the song CRISPR-Cas9

Efficient delivery of CRISPR remains THE challenge

[coldandcalculating]

While it's important the continue testing the limits of CRISPR technology in preclinical studies like this, the truth is that viral vector based delivery isn't quite up to the challenge (yet!) of a total genomic clearance of HIV in all infected cells. From the news and views comment on the article:

several issues remain to be addressed prior to clinical trials. While an AAV serotype with broad tropism is ideal for proof-of-concept studies, replication competent HIV is rare (present only in one of every 10,000 to 1,000,000 CD4+ T cells), and thus identifying delivery vectors with high specificity to the HIV reservoir remains a significant hurdle. There is currently no known viral or non-viral agent that is capable of efficiently and selectively delivering and expressing transgenes in these cells. An ideal delivery candidate should possess the ability to carry a relatively large cargo to relevant reservoir cells and facilitate pharmacologically significant enzymatic activity. It should also exhibit little to no toxicity irrespective of the duration of its presence in vivo, whether transient or long term.

(emphasis mine)

Still, this is a very encouraging development toward a possible HIV cure.

Re:And the cost....

[0123456]

In a few years, the cost will be $10 plus a flight to Mexico.

Or $10,000,000 if you want the treatment America.

CRISPR has potential application for flu

[SethJohnson]

This system would not be useful for treating any virus that doesn't use DNA (like, say, the flu)....

Per this article in Scientific American--

...But until the arrival of CRISPR, virologists lacked the tools to easily alter ferret genes. Xiaoqun Wang and his colleagues at the Chinese Academy of Sciences in Beijing have used CRISPR to tweak genes involved in ferret brain development, and they are now using it to modify the animals' susceptibility to the flu virus. He says that he will make the model available to infectious-disease researchers.

Note the open-source mindset already beginning to surround CRISPR! Researchers are exchanging their CRISPR recipes without concern for patents and intellectual property. This can really accelerate progress with developing CRISPR-based treatments.