"Scientists eliminate HIV-1 from genome of human T-Cells"

[tryingtostay]

Hang in there people.

Link


A specialized gene editing system designed by scientists at the Lewis Katz School of Medicine at Temple University is paving the way to an eventual cure for patients infected with HIV, the virus that causes AIDS. In a study published online this month in the Nature journal, Scientific Reports, the researchers show that they can both effectively and safely eliminate the virus from the DNA of human cells grown in culture.

According to senior investigator on the new study, Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University (LKSOM), "Antiretroviral drugs are very good at controlling HIV infection. But patients on antiretroviral therapy who stop taking the drugs suffer a rapid rebound in HIV replication." The presence of numerous copies of HIV weakens the immune system and eventually causes acquired immune deficiency syndrome, or AIDS.

Curing HIV/AIDS—which has claimed the lives of more than 25 million people since it was first discovered in the 1980s - is the ultimate goal in HIV research. But eliminating the virus after it has become integrated into CD4+ T-cells, the cells primarily infected with HIV, has proven difficult. Recent attempts have focused on intentionally reactivating HIV, aiming to stimulate a robust immune response capable of eradicating the virus from infected cells. However, to date, none of these "shock and kill" approaches has been successful.

Dr. Khalili and colleagues decided to try a different approach, specifically targeting HIV-1 proviral DNA (the integrated viral genome) using uniquely tailored gene editing technology. Their system includes a guide RNA that specifically locates HIV-1 DNA in the T-cell genome, and a nuclease enzyme, which cuts the strands of T-cell DNA. Once the nuclease has edited out the HIV-1 DNA sequence, the loose ends of the genome are reunited by the cell's own DNA repair machinery.

In previous work, Dr. Khalili's team had demonstrated the ability of their technology to snip out HIV-1 DNA from human cell lines. In their latest study, however, they concentrated on latently and productively infected CD4+ T cells to show not only that the technology eliminates the virus from cells but also that its persistent presence in HIV-1-eradicated cells actually protects them against reinfection. More importantly, they carried their work over to ex vivo experiments, in which T-cells from patients infected with HIV were grown in cell culture, showing that treatment with the gene editing system can suppress viral replication and dramatically reduce viral load in patient cells.

In another major component of the study, Dr. Khalili's team addressed questions about off-target effects and toxicity. Using an approach known as ultra-deep whole-genome sequencing, which is considered the gold standard for genomic assessment, the researchers analyzed the genomes of HIV-1-eradicated cells for mutations in genes outside the region targeted by the guide RNA. Their analyses ruled out off-target effects on genes, including potential collateral effects on cellular gene expression. Studies of cell viability and proliferation showed that HIV-1-eradicated cells were growing and functioning normally.

"The findings are important on multiple levels," Dr. Khalili said. "They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4 T-cells and, by introducing mutations into the viral genome, permanently inactivating its replication. Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects."

"These experiments had not been performed previously to this extent," he added. "But the questions they address are critical, and the results allow us to move ahead with this technology."

[Ptrk3]

Thanks for posting.  I saw this online earlier today, but couldn't get a perspective of this effort and how it may relate, if at all, to other seemingly similar efforts:  that is, how do some of the other "gene editing/slicing" approaches fit in with this one and can they collectively build to some sort of "eureka" moment?

It does seem promising, though, that so much of this type of research is going on.  Can any forum member give a sense of how important this research is and what it may mean for a possible "functional" or "sterilizing" cure?  Is this type of research going to take years or decades before it can be practically used a human trial?

[tryingtostay]

I also was curios what method they were using too.  The few I know are Brec1, CRISPR, ... and something else. 

[PittGurl]

Yes, def following this thread! Would love to hear insight from LTS!

[Ptrk3]

Interesting how these stories make their way through the media.  Here's the same story originally posted in this thread, posted today with a more optimistic headline (and I thought that Americans were supposed to be more optimistic than the Brits!):

http://www.telegraph.co.uk/science/2016/04/01/cure-for-hiv-possible-within-three-years-as-scientists-snip-viru/

Hang on, Sloopy!  Three more years and we're good to go:

https://www.youtube.com/watch?v=GG2qVcff04g

[tryingtostay]

I wonder if it applies to the tissues and cells in our brains as well as the other tissue layers HIV permeates.  Or if it can penetrate the Central Nervous System. 

[tryingtostay]

http://www.telegraph.co.uk/science/2016/04/01/cure-for-hiv-possible-within-three-years-as-scientists-snip-viru/

Interesting.  In this article the writer mentions Crispr while the other doesn't.  I thought Crispr had a long way to go?  Brec1 was suppose to be better than Crispr and it still is in testing AFAIK.  correct me if I am wrong

[bmancanfly]

These threads are always amusing.  You realize that this was a test done in a Petri dish right? If it gets regulatory approval and if they find the funds to continue, it would take years and years for human trials to begin.  Then if everything goes perfectly, the trials process would also take years and years.  And that assumes no setbacks along the way.  And what could possibly go wrong when you alter someone genes inside their body? 

Anybody who thinks that this will be a cure available in 3 years,  contact me, I have a bridge in Brooklyn I can sell you real cheap.  Hurry while supply lasts. 

A healthy interest in science is a good thing.  But hawking every discovery made in a test tube or Petri dish as the "cure du jour" and raising the expectation that the end of HIV is near, isn't a very healthy use of time, or a realistic assessment of the state of the science.

An HIV infection is a life long commitment and will remain so for the foreseeable future.  Sorry to be a buzz kill,  but that's just the way it is right now.

[tryingtostay]

You cannot deny this is exciting news.  This is different than all tests in labs in the past.  It's the same old excitement and promise type article but this is a whole new level and different approach.  And I hear you.  And it's perfect reasoning seen through the eyes of experience. 

Thanks for the amusement.

[Ptrk3]

True, bmancanfly, a "sterilizing" cure is a long way off--decades probably, and the headline to the story does not match the story (the story says no such thing that a cure is three years away--just human trials, but, alas, copyeditors write the headlines), but the story is newsworthy nonetheless in a "Research News and Studies" section of the Forums.  It's nice to build a record of these studies in one place, just so folks can see that there's much research being done.

[freewillie99]

Having followed the various gene therapy approaches over the last 10 years or so, e.g. Sangamo, Calimmune, etc., this latest advance strikes me as very good news. Of course the hyperbolic headlines (3 years to a cure!) are pretty dumb, but I guess that's what sells and attracts eyeballs.

There has been success prior to this editing various cells to be HIV resistant, but marrying a scissor-like enzyme to a guide RNA is something I hadn't come across before in an HIV treatment. Pretty cool, but the fact that this is done in vivo, unlike the other prior treatments which were done ex vivo, may make the FDA a bit extra cautious when moving forward with this. Anyway, sounds like they'll be testing it in humanized mice and chimpanzees / macaques in the near future, so keep your eye on the news in a few months to see what sort of press releases come out.

Cautious optimism and hope for the best. You never know; this could be a big deal at some point.

[zettainaoru]

I really hope it works in human.
Safety issues probably gonna be first.
Just hope it wont cut the wrong DNA.

Woww.... we are at DNA editing century now.....  (Well, theres that GMO things, but this is different).
cool!!!!!!

[Skydrake]

Interesting how these stories make their way through the media.  Here's the same story originally posted in this thread, posted today with a more optimistic headline (and I thought that Americans were supposed to be more optimistic than the Brits!):

http://www.telegraph.co.uk/science/2016/04/01/cure-for-hiv-possible-within-three-years-as-scientists-snip-viru/

What a ridicolous article.
Absolutely impossibile to have a cure within three year!!!!
Until now, experiments have so far only been carried out in a lab.
Maybe 3 years to the Phase I to humans.
Phase I + Phase II + Phase III = 7-10 years.

[Jim Allen]

I personally think UK media is a utter disgrace anyway, not sure why anyone bothers reading anything printed or reported from the UK anymore. 

Noticed POZ.com have a story on this "cure" claim.
Media Outlets Falsely Claim That a Cure for HIV May Be Only Three Years Away
https://www.poz.com/article/media-outlets-falsely-claim-cure-hiv-may-three-years-away

"“Cure for HIV possible within three years as scientists snip virus from cells,” The Telegraph’s headline touts. Posted on April 1, the article was no April Fool’s Day prank. Its incorrect claim has fanned across the Internet, parroted by Fortune, Fox News, AOL News and various others."

""This is not the first time The Telegraph has spawned a rash of hyperbolic and inaccurate reporting about the supposed imminence of an HIV cure. In April 2013, the publication erroneously claimed that Danish researchers were “mere months” from finding a cure for the virus. In that case the report concerned a cure therapy that was only in Phase I human trials."

[Skydrake]

I personally think UK media is a utter disgrace anyway, not sure why anyone bothers reading anything printed or reported from the UK anymore. 

Noticed POZ.com have a story on this "cure" claim.
Media Outlets Falsely Claim That a Cure for HIV May Be Only Three Years Away
https://www.poz.com/article/media-outlets-falsely-claim-cure-hiv-may-three-years-away

"“Cure for HIV possible within three years as scientists snip virus from cells,” The Telegraph’s headline touts. Posted on April 1, the article was no April Fool’s Day prank. Its incorrect claim has fanned across the Internet, parroted by Fortune, Fox News, AOL News and various others."

""This is not the first time The Telegraph has spawned a rash of hyperbolic and inaccurate reporting about the supposed imminence of an HIV cure. In April 2013, the publication erroneously claimed that Danish researchers were “mere months” from finding a cure for the virus. In that case the report concerned a cure therapy that was only in Phase I human trials."

This is the reaction of dr. Kamel Khalili, director of the researching team:



And this is the counter-reaction on Twitter of Sarah Knapton, the journalist of Telegraph:  block the account of the POZ journalist who requested for corrections

https://twitter.com/TAGHIVscience/status/717049235426947073
 

[Almost2late]

HIV overcomes CRISPR gene-editing attack
Virus can quickly develop mutations that resist attack by DNA-shearing enzymes.

Ewen Callaway
07 April 2016
Article toolsRights & Permissions

National Institutes of Health/Stocktrek Images/Getty Images
Researchers hope to use CRISPR gene-editing to prevent HIV entering a T cell (pictured, scanning electron micrograph) — or to disable the virus once it has infected the cell.
HIV can defeat efforts to cripple it with CRISPR gene-editing technology, researchers say. And the very act of editing — involving snipping at the virus’s genome — may introduce mutations that help it to resist attack.

At least half a dozen papers over the past three years have explored using the popular CRISPR-Cas9 gene editing technique to combat HIV, but the latest finding, described in a study published on 7 April in Cell Reports1, adds to questions about the feasibility of the approach. However, the researchers involved say that the discovery is a minor setback that does not preclude the idea altogether.

Some researchers aim to edit genes made by the immune cells that HIV usually infects — called T helper cells — so that the virus cannot find a way in. Others take a different tack: equipping the T cells with gene-editing tools so that they can seek and destroy any HIV that infects them.

Read whole story here...
http://www.nature.com/news/hiv-overcomes-crispr-gene-editing-attack-1.19712

[zettainaoru]

 
sad news

[tryingtostay]

It looks more and more like defeating HIV will be a multi prong approach.  From the article: "Liang doesn't believe the effort is futile, however, as there are strategies that could overcome this limitation. For example, targeting multiple sites with CRISPR/Cas9 or using other enzymes aside from Cas9. Once a solution is identified, the next barrier will be identifying ways to deliver the treatment to patients.

"CRISPR/Cas9 gives a new hope toward finding a cure, not just for HIV-1, but for many other viruses," Liang says. "We have a long road toward the goal, and there may be many barriers and limitations that we need to overcome, but we're confident that we will find success."

More info on the resistance to CRISPR: Link

[CaveyUK]

sad news

I don't know about that.

Finding that something doesn't work or is less likely to work only furthers knowledge and re-focuses cure/vaccine/treatment research on areas that have more promise.

There are a lot of good people doing a lot of good work in the research world in relation to HIV and other conditions. If finding things don't work allows these people to focus on areas which may work, I'm all for it.

[Hoyland]

For those interested in the science.

http://www.ncbi.nlm.nih.gov/pubmed/27013255

[RobbyR]

Let's hope they find a CURE soon. So then millions of us won't have to take meds every single day any more & deal with the stigmas, &the pharmaceutical industry won't be able to continue making billions in profits off of the drugs. How liberating it will be when the cure finally comes!

[CaveyUK]

Let's hope they find a CURE soon. So then millions of us won't have to take meds every single day any more & deal with the stigmas, &the pharmaceutical industry won't be able to continue making billions in profits off of the drugs. How liberating it will be when the cure finally comes!

I don't care about how much money the drug industry makes as long as treatments are readily available for all and work.

Equally, I'm really not too bothered about not having to take a tiny pill once a day. Chances are, as we age, it won't be the only once-a-day pill you will have to take!

As for stigma, well - even if they do find a way of 'curing' HIV, the antibody will still be there I suspect, so people will still test 'HIV positive'. The best hope is that over time, education increases and the treatment of the condition becomes so routine, so mundane that it is viewed by people in the same way Herpes is.

[harleymc]

That was one of the fastest "now you see it now you don't, disappearing cures" I've seen in over 30 years.

Glad I didn't blink.

[zettainaoru]

As for stigma, well - even if they do find a way of 'curing' HIV, the antibody will still be there I suspect, so people will still test 'HIV positive'. The best hope is that over time, education increases and the treatment of the condition becomes so routine, so mundane that it is viewed by people in the same way Herpes is.

I think Timothy brown had far less HIV antibody now. I forgot where i read it.
It seems if the virus is not in your body anymore the antibody gradually disappear. Just like for flu virus.

The science behind this research is wowwww......
With this science, they can just put some DNA code of Neutralizing antibody in body tissues, and then cut it out of the body tissues after cured.

[MattNY]

For those interested in the science.

http://www.ncbi.nlm.nih.gov/pubmed/27013255

Thanks.