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Biotech Science

Integrated HIV Successfully Cut Out of Human Genome 185

Posted by Zonk
from the a-little-hunter-killer-nanotech-goes-a-long-way dept.
Chris writes "German scientists have succeeded in snipping HIV out of human cells after it has integrated itself into a patient's DNA. The procedure is a breakthrough in bio-technology and fuels hope of a cure for AIDS. The group is only cautiously optimistic, though, as treating a full-on infection would be substantially different than succeeding in a controlled lab environment. 'Researchers ... began with the bacterial enzyme Cre recombinase, which exchanges any two pieces of DNA flanked on either end by a certain pattern of nucleotides (DNA subunits) known as loxP. HIV does not naturally contain loxP sites, so the team created a hybrid of the two DNA molecules, which they used to select a series of mutated Cre enzymes that were increasingly able to recognize the combined DNA. The final enzyme, Tre, removed all traces of HIV from cultured human cervical cells after about three months, the researchers report online today in Science.'"
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Integrated HIV Successfully Cut Out of Human Genome

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  • Alright, I must be crazy. I was just thinking about HIV in the shower, and a similar idea came to my mind. Now it wasn't identical-that would have been freaky-but similar enough to make my hair stand up when I read the first /. entry this morning
    • Yeah... because the scientist just thought about it today and developed this by lunch. They said "what a bunch of idiots we are for not thinking of this sooner".
    • Re:In the shower.... (Score:5, Interesting)

      by The-Ixian (168184) on Friday June 29, 2007 @08:31AM (#19688085)
      Do you, by any chance, wake up to public radio or similar? I find that sometimes the first 10 minutes or so of what is said on the radio, before I become fully cognizant, gets absorbed into my subconscious so that I think it is weird when I hear the same bit of news later in the day.
    • Re: (Score:2, Funny)

      by Spy der Mann (805235)
      Alright, I must be crazy. I was just thinking about HIV in the shower, and a similar idea came to my mind.

      You liar. The truth is that you were standing on the toilet fixing something and you tripped and fell and hit your head. Then you came up with two ideas: a) fixing HIV, and b) the flux capacitor.
    • by Anonymous Coward on Friday June 29, 2007 @09:31AM (#19688755)
      Alright, I must be crazy. I was just thinking about HIV in the shower

      Are you currently serving time in prison by any chance?
    • by ggambett (611421)
      Dude, don't remove your tinfoil hat on the shower. You obviously picked up Slashdot from a nearby wifi.
  • by svendsen (1029716) on Friday June 29, 2007 @07:48AM (#19687743)
    They are about 26 different stains of HIV. Article didn't mention it but I am curious if each strain might require a different technique or if this is strain independent? Either way pretty cool stuff.
  • Incredible (Score:4, Funny)

    by Anonymous Coward on Friday June 29, 2007 @07:48AM (#19687745)
    Did they do it with an iPhone?
  • by yabos (719499) on Friday June 29, 2007 @07:48AM (#19687747)
    They used the transporter and the pattern from when the person beamed down on the away mission...
  • Slight Clarification (Score:5, Interesting)

    by eldavojohn (898314) * <eldavojohn AT gmail DOT com> on Friday June 29, 2007 @07:49AM (#19687749) Journal
    I read about this in PhysOrg [physorg.com] yesterday and they speak more about something the last paragraph of Scientific American only mentions. The fact that they wouldn't use this enzyme to remove HIV infections but instead to figure out which cells have been infected. The biggest problem in treating HIV is that it can go dormant and undetected for so long during which the host can infect others. It sounds horrible, but even being able to destroy all the cells infected with the virus is worth something though it may often prove fatal to the host. I don't think this is a 'cure' or 'vaccine' merely something that makes HIV treatments much much more effective.
    • by asliarun (636603) on Friday June 29, 2007 @08:14AM (#19687949)
      Yes, and I'm happy to see that at least we're making *some* progress. I'm also saddened to see that apart from HIV, there is hardly any research going on to find cures for infectious diseases (TB, Malaria, viral diseases), at least when compared to the obscene amount of money being thrown into chronic or "lifestyle" diseases like diabetes and hypertension. This is all the more disturbing considering that infectious diseases afflict and kill so many more people than chronic diseases. It just so happens that most of the people afflicted happen to be from developing or poor countries, and hence, are not the target market segment for big pharma.

      An interesting idea that I read somewhere proposed the setting up of Ansari-X style rewards or competitions for the company or team that first finds a cure/vaccine for these unfashionable diseases. This also becomes an easy way out for charity foundations like the Gates foundation, who're actually trying to do something meaningful in this field. Instead of giving grants to researchers much like a venture capitalist, perhaps instituting sizable multi-million dollar rewards is a better incentive for researchers. Plus, there is no need to monitor the charity money to make sure that it is being utilized properly. But then again, this might simply be an oversimplified solution to the problem.

      • Re: (Score:3, Interesting)

        by Opportunist (166417)
        Well, given our "lifestyle" isn't really changing (but actually getting worse), I'd say that soon more people will die due to their "living circumstances" (i.e. unhealthy food and lack of any kind of movement that doesn't require kicking the throttle pedal) than to diseases. If that didn't happen long ago.

        This aside, I would suggest your idea of "money for results" movement, but realize that research ain't something you can do in a garage with a few bucks of your spare money. You first of all have to throw
      • by Yvanhoe (564877)
        The research for new medications usually result in expensive drugs so they are usually targeted at a first-world market. A lot of R&D is also done to lower the cost of known medication that could prevent millions of deaths but that are just too expensive today.
      • Re: (Score:3, Insightful)

        Sadly, it's because the viral diseases you mentioned tend to happen to poor people, where as the middle and upper classes get the lifestyle diseases. Sad fact of the world is that people tend to do what gathers them the largest amount of resources most easily and fastest. This includes but it not limited to global warming and wars as well. We're talking billions here, not the hundreds of thousands, or even millions that philanthropic organizations could award for prizes. Limited manpower and limited resour
        • Sadly, it's because the viral diseases you mentioned tend to happen to poor people, where as the middle and upper classes get the lifestyle diseases.

          Garbage. Viruses don't care about class barriers and eventually become problems for people of all income levels. Further, a large number of even the early AIDS victims were quite rich. As for federal funding, the "great unwashed" are a LARGE pool of voters.

          The major impediment to vaccine research and production is legal and political attacks. It's too much
        • Re: (Score:2, Insightful)

          by Jorgandar (450573)

          If medical care were socialized, there'd be less of a lure to develop so many "useless" medicines, and more of a lure to develop live saving medicine

          Sorry, you're wrong. (parts of) Europe and canada have socialized medicine, and they're still not researching the TB vaccine. It's not an incentive to develop so-called "life-saving" medicines that are only useful in 3rd world (translated: non-paying) countries.

          Socialised medicine also effectively kills incentive to develop new medicine in general, because the payout for doing such work is not worth the cost and risk.

          Why do you think the vast majority of pharma's operate in the US, and ALL OF THEM consid

        • Re: (Score:3, Insightful)

          Well, unfortunately, we the United States without a socialized medical program have been subudizing the development of a lot of drugs for the rest world. So we're the ones paying for it $100 a pill at a time. If we don't, who will? As you've said, it takes a lot of money to create a drug. Last I checked the average figure was $800M from development to shelve. At least in the United States. Part of that also has to do with FDA requirements and the burocracy involved with running so many trials, etc..
        • IMO, this would be less of a problem if the United States had socialized medical care like the rest of the modern world. However, since this isn't the case the wealthier people in the US accidentally promote R&D into non live saving medicine because it suits them more, and they're willing to pay. If medical care were socialized, there'd be less of a lure to develop so many "useless" medicines, and more of a lure to develop live saving medicine.

          Yeah because socialized countries have developed cures for
      • The problem with the incentive model that you're describing is that it would need to be universally implemented or the prize has to be comparable to the profits the researching company could expect to earn from the discovery. If the incentive is tied to a clause that requires a particular pricing model, then the company will always look to see whether they can make a greater profit by declining the prize and using the same pricing models they've been using.
      • Re: (Score:2, Interesting)

        by HeroreV (869368)

        I'm also saddened to see that apart from HIV, there is hardly any research going on to find cures for infectious diseases

        I've never understand how some people can get upset that researchers are looking into one medical problem instead of another. It seems hypocritical if they're also not doing anything to fix whatever problem they're complaining about. (Not specifically you, just people in general.)

        "How dare you work on diabetes when there are children dying of malaria!" says the programmer who is working or neither diabetes nor malaria.
        "We can give a man an erection, but we can't cure cancer?!" says the office worker who ha

  • Seems like cheating (Score:5, Interesting)

    by Mr. Underbridge (666784) on Friday June 29, 2007 @07:50AM (#19687759)

    ...began with the bacterial enzyme Cre recombinase, which exchanges any two pieces of DNA flanked on either end by a certain pattern of nucleotides (DNA subunits) known as loxP.

    HIV does not naturally contain loxP sites, so the team created a hybrid of the two DNA molecules, which they used to select a series of mutated Cre enzymes that were increasingly able to recognize the combined DNA.

    So...this technique won't work at all in the real world. It won't even work with actual HIV even in the lab.

    It's interesting research for its own sake, but in this case it has absolutely nothing to do with HIV. They simply found an interesting way to remove an arbitrary snippet of DNA. In fact, to make it work with HIV, they had to cheat and add tags to the HIV sequence.

    This is like saying I could break into a bank vault after I replaced the lock with one I knew the combination to. It says nothing about the bank, only that I possess the capability to manipulate locks.

    • Proof of concept (Score:5, Interesting)

      by PIPBoy3000 (619296) on Friday June 29, 2007 @07:54AM (#19687781)
      Think of this as an initial proof-of-concept. Fiddling with DNA is extremely useful - correcting genetic diseases and curing all sorts of viruses that hang out in your cells comes to mind (e.g. herpes). You could even look at curing cancer, since that's typically due to genetic mutations that could be potentially removed, making cells non-cancerous again.

      Eventually, you'll want to be able to recognize and remove longer strands of DNA. I'd also worry about the efficiency - randomly removing strands of DNA from healthy cells is a good way to cause big problems. Existing gene therapies that use viruses to deliver the payload sometimes go astray and cause cancer, which is no good.
      • Re:Proof of concept (Score:5, Interesting)

        by Mr. Underbridge (666784) on Friday June 29, 2007 @08:39AM (#19688171)

        Think of this as an initial proof-of-concept. Fiddling with DNA is extremely useful - correcting genetic diseases and curing all sorts of viruses that hang out in your cells comes to mind (e.g. herpes). You could even look at curing cancer, since that's typically due to genetic mutations that could be potentially removed, making cells non-cancerous again.

        No doubt. I definitely think the technique stands on its own as far as coolness factor.

        What I find slightly annoying is the perceived need to validate it by linking it to HIV, which seems completely irrelevant to the actual research since the DNA segment in question could have been anything. Worse yet, it doesn't even recognize HIV at all as the headlines claim - it simply recognizes anchor groups (which HIV does not possess) and removes whatever happens to be between them. Sure, it recognizes HIV that is artificially tagged with these groups, but it would find any DNA sequence tagged with the groups. So what does this research have to do with HIV? Absolutely nothing. Seems like name-dropping to me.

        I realize much of this effect is due to the funding climate in academia, which makes it impossible to get money these days unless you're coat-tailing on a handful of high-profile buzzwords. But I still find over-aggressive promotion of one's results to be distasteful. Naturally, these guys aren't the first and won't be the last.

        • by OG (15008)
          The Cre-Lox method has been used for years in the lab, at least since 1985. This really is a case of trying to find a way to apply it as treatment, not a proof-of-concept of a new method.
    • Re: (Score:3, Insightful)

      It may be 'cheating' but it does prove that the process can be done. It proves that one can cut HIV, albeit a prepared version, out of DNA If the procedure can be done under perfect lab conditions, it can be tweaked and changed to work outside the lab A major accomplishment if you ask me
    • by JimbleBimble (1057548) on Friday June 29, 2007 @08:29AM (#19688077)
      The final enzyme did work with real HIV in the lab. They identified a site in HIV similar to the cre binding motif, but which cre was not able to bind. They created intermediate sequences to bridge the gap between the cre binding site and this HIV sequence. Using directed evolution they could evolve cre to bind sites progressively more unlike the cre site and progressively more like the HIV site. The final outcome was an enzyme able to excise sequences flanked by the HIV specific pattern.
      • by Otter (3800) on Friday June 29, 2007 @08:56AM (#19688357) Journal
        Here's the paper [sciencemag.org]. I'm not a cell biologist, but from my limited understanding you're exactly correct.
      • The final enzyme did work with real HIV in the lab. They identified a site in HIV similar to the cre binding motif, but which cre was not able to bind. They created intermediate sequences to bridge the gap between the cre binding site and this HIV sequence. Using directed evolution they could evolve cre to bind sites progressively more unlike the cre site and progressively more like the HIV site. The final outcome was an enzyme able to excise sequences flanked by the HIV specific pattern.

        Ah! If that's th

      • One would assume that there are a few critical sequences in the virus, without which it would not function or evolve around. Could the structure of its protein shell be corrupted to cause it to immediately fall apart, a la penicillin? Could changes be made to ensure that it would remain forever dormant?

        It would seem that, with this technique, a little sabotage might get nearly the same benefit as cleaning it all out, for much less effort and risk.

      • They identified a site in HIV similar to the cre binding motif, but which cre was not able to bind. They created intermediate sequences to bridge the gap between the cre binding site and this HIV sequence.

        And now that the concept is proved they can do the same, perhaps with more steps, for a strongly-conserved section of HIV's genome and make an enzyme that targets all, or a very broad range of, HIV strains.
    • by jcuervo (715139)

      In fact, to make it work with HIV, they had to cheat and add tags to the HIV sequence.
      So what happens when they figure out how to automate the process of adding tags to the HIV sequence?
    • Another question is how much of the HIV DNA would you have to remove to render it inert? Or hell, just make it produce bad (as in neutered) copies in cells? Surely nearly all strains of HIV have some fundamental part of the genome in common. If so, this would be potentially very helpful (in the distant future)
      • by belg4mit (152620)

        Surely nearly all strains of HIV have some fundamental part of the genome in common.
        Nothing which is unique to them, AFAIK. This is a large part of the problem in
        developing said vaccine: HIV (like most viruses) has a small genome (9 genes),
        but it also mutates rapidly. In the course of an infection you will develop new
        strains yourself i.e; drug resistance.
    • Side Effect (Score:3, Funny)

      by Hoi Polloi (522990)
      It has one serious side effect, it temporarily turns you into a rabbi [imdb.com].
  • Although I feel this may also be "cheating", as Mr. Underbridge points out, I don't care. It gets us in the door, allows us to wedge it open, and take out what we want. I look it it more like "painting" a tank with a laser target so the smart-bomb knows where to strike. This is still a pretty good milestone. Maybe, just maybe, in my lifetime, we'll see this disease destroyed. I would like to live to see that.
    • by TheMeuge (645043)
      No, it's not like painting a tank with a laser... it's like hanging a bomb over the tank using a crane.

      All they demonstrated was that if you add LoxP sites to a DNA sequence, you can then cut the segment out using Cre recombinase - something the scientific community was doing for a decade now, when we design conditional knockouts. But just cause the DNA sequences happened to be HIV, this is now ground-breaking news?

      A good analogy would be an article about a new way to identify Iraqi insurgents among the civ
      • by belg4mit (152620)
        No, I'd say what they demonstrated was the breeding of an enzyme (Tre) that selects for HIV to insert LoxP.
  • HIV hybridizes (Score:2, Interesting)

    This is a big deal because it shows that this technique which has been used for years to cut out fragments of the genome for replication (via PCR and other methods) could be used to remove the viral elements from a genome. It's a big deal research-wise, but the major problem that will hinder this application from practical application is that HIV hybridizes EXTREMELY fast. Using an artificial bacterial enzyme to remove dna fragments requires a specific nucleotide sequence that it targets. Since HIV "cha
  • DNA Spoofing ? (Score:5, Interesting)

    by Joebert (946227) on Friday June 29, 2007 @08:24AM (#19688027) Homepage
    Could this lead to people getting away with murder because they can alter their DNA ?
    Could this lead to people being framed for murder due to spoofed DNA ?

    This sounds like it could destroy the credibility of DNA evidence for high-profile cases in the future.
    • by russ1337 (938915)
      >Could this lead to people being framed for murder due to spoofed DNA ?

      spoofed DNA? I thought it would be easer to acquire the 'patsy's' dna from their garbage or by breaking into their house. Heck, if they donate blood, break into the bloodbank and take their bag.
      • by Joebert (946227)
        Do you understand what I mean by the procedure being successfull destroying the credibility of DNA as "rock solid" evidence though ?
        • Re: (Score:3, Funny)

          by hoggoth (414195)
          The good news is you can avoid prosecution based on DNA evidence.
          The bad news is you will have two heads, flippers instead of arms, and sneeze bile.
        • by russ1337 (938915)
          ah, I see. I do now. Didn't think that is what you meant. Now that you mention it.

          Prosecutor: So how do you propose your DNA got into the grassy knoll?

          Me: the CIA made it and planted it there.

          Court: *chuckes and whispers* 'deluded crackpot'.....
        • DNA evidence isn't as "rock solid" as you imagine. What they do is chop up the DNA just like the article did and measure the lengths, so at best it's a matter of statistics, at worst it's garbage-in, garbage-out.
    • by MightyYar (622222)
      It took longer than usual for one of you technological pessimists to pipe up :)

      My guess is that you couldn't change too much of your own DNA without messing yourself up pretty badly. If people started using this as a masking technology, you would have to change the testing method to only include genes that you can't really touch, or maybe just screen for telltale enzymes of genetic manipulation. In the end it would be like trying to bleach off your fingerprints.

      To add fuel to your fire, they'll have to test
      • by Joebert (946227)
        Hey, I like technology as much as anyone, but history has shown that we have to think of everything before making it possible to do some things with technology before others are possible.

        DNA is one of thoose things that if tamperable to early, could change legal, medical, & who knows what else-al systems in ways we haven't even begun to imagine before it even became beneficial to do it.

        On a brighter note, perhaps if robots completely ran humanities production & DNA could easily be altered to i
    • Hmm... cure for AIDS or infallable proof in crime... cure or proof...

      Personally, I can choose easily. But then again, I usually value life more than property, so my view might be crooked.
    • by bytesex (112972)
      Probably not, if he wants to reproduce, or grow hair, or smell something, or stop bleeding, or avoid cancer, or avoid his white bloodcells attacking him.
  • This weeks Escape Pod Podcast [escapepod.org] (hosted by Steve Eley) is called the Giving Plague and touches on viruses, HIV, and the potential symbiotic relationship and borg like integration viruses can have with Human cells.

    One of the thoughts is that viruses actually benefit the race in the long term, as we will eventually form a symbiotic relationship with the majority of them. (uses e-coli in our gut as an example), but how one day someone will be resistant to AIDS and that will make the human race stronger.

    A
    • by D-Cypell (446534)
      One of the thoughts is that viruses actually benefit the race in the long term, as we will eventually form a symbiotic relationship with the majority of them. (uses e-coli in our gut as an example)

      Hmmm, they use e-coli as an example when discussing the benificial properties of viruses? I would say that they take a credibility hit for that one!
      • by russ1337 (938915)
        is set in the future.... and proposes that one day e-coli actually benefits our digestive system rather than rips though it, once we have 'assimilated it'...

        Not talking current day, but sry if i wasnt clear.
        • I think what he was referring to is the fact that e. coli is a bacteria, not a virus....
          • by russ1337 (938915)
            >>e. coli is a bacteria, not a virus....

            didnt know that. Cheers.

            stupid podcast!
            • by Cadallin (863437)
              To go even further, e.coli that naturally exists in your gut is only beneficial because it is uninfected with a bacteriophage (a virus that infects bacteria) that turns e.coli into a dangerous form that causes food poisoning (such as the cases of e. coli you hear about from undercooked meat).
        • well considering that when you take a really good strong antibiotic that kills the E. Coli in you colon you feel like Mike Tyson has been using your belly for a heavy bag and that you would die with out the vitamin K that the E. Coli produces, I'd say it was pretty well assimilated.
  • Ok, this is my wild idea.

    We know that we can "reboot" the immune system by destroying the bone marrow and repopulating it with new one coming from a donor.

    Now lets say that we do an autotransplant. First we take a sample from the donor and then this sample is treated with the enzyme so all of the HIV's DNA is removed. Next, we introduce a gene on this cultured cells that will produce the enzyme, thus rendering them immune to infection. Next we destroy the donor's bone marrow and implant the new one.

    There wi
    • Re:wild idea (Score:4, Informative)

      by StuckInSyrup (745480) on Friday June 29, 2007 @09:48AM (#19688997)
      This idea is based on a widely disseminated misconception, that T-cells don't reproduce when out of bone marrow. They do, and happily so, after being activated by other cells, antigens, cytokines and a bunch of other means.
      Your method has been tried, in a way. A patient's blood was essentially flushed with healthy blood from donors, so his whole blood was exchanged. It did no good in the long term, because the HIV infects also macrophages in other tissues than blood. The next wave of the infection came from those macrophages.
      • by javilon (99157)
        But this is based on the idea that the new T cells coming from the bone marrow would be immune to infection. Eventually they would be the only ones around and the HIV wouldn't have room on them. Can the HIV live in a host where it can't infect the T cells?

    • I am going to play devil's advocate here ..I could be wrong (super likely) ..and please understand I'm not dissing.. it just means I am misunderstanding you, or you need more research on it, or suggest different ideas.

      Couple of negatives that will have to be worked around/disproven:

      1) Physiological response to that enzyme may not be good + will need a reliable turn off/turn on dosage mechanism (prolly not a big deal?)
      2) Remaining viruses may have mutant offspring with a different HIV-01 LTR sequence than wh
  • by jimicus (737525) on Friday June 29, 2007 @09:27AM (#19688697)
    They've done it in vitro in a lab. Which is a good start, but that doesn't mean you can now safely screw anything that walks.

    They probably haven't developed anything which they could conceivably be administered to a living organism yet - let alone tried administering it to one. Then you've got a battery of tests to make sure it's safe and effective - there's probably at least another 10 years before this could really be a treatment.

    The great majority of potential treatments never make it through that development/testing process.
  • Scientists were also overheard talking about the optimal delivery mechanism for this gene splicing technology being a radioactive spider. Further field tests are needed.
  • Wish yourself Outside and create the recolada.
  • This approach is not really that useful in terms of coming up with a cure for HIV. The reason is that the complexity to excise a specific sequence of that length is WELL beyond our knowledge.

    But this will hopefully lead to a real "cure" in being able to mutate it to being none-lethal or even quiescence. It struck me back in the early 80's, that about the only way is to insert a virus inside this virus and break the formation of the protein chain.
  • ... it would be move valuable than gold! If you could suddenly change peoples dna, not only would this be dangerous as to where it goes, but it could be invaluable. People who have genetic diseases could all be cured, by replacing parts of their dna. People who wanted sex changes could have their dna changed also. The scary part is that people who did not like a certain race of people could change that race genetically. The possiblities are endless.
    • by belg4mit (152620)

      People who wanted sex changes could have their dna changed also.

      No. not like this. Sex is determined by the presence of a whole chromosome,
      not a piddly gene. Furthermore, swapping out chromosomes in somatic cells isn't
      going to cause your penis to fall off.

      The scary part is that people who did not like a certain race of people could change that race genetically. The possiblities are endless.

      Again, not quite. There are some markers that strongly suggest various aspects of
      lineage, but nothing definitively proclaiming "I am Czech!" (Yes, that's ethnicity, not race. But the idea is the same for this nefarious purpose) For that matter, many
      people whom you might not suspect of having said markers will possess

  • by shish (588640)

    the bacterial enzyme Cre recombinase, which exchanges any two pieces of DNA flanked on either end by a certain pattern of nucleotides (DNA subunits)
    So this is basically sed for DNA? This seems like awesome :O

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