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Integrated HIV Successfully Cut Out of Human Genome

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.'"

19 of 185 comments (clear)

  1. Different Strains? by svendsen · · Score: 4, Insightful

    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.

  2. Incredible by Anonymous Coward · · Score: 4, Funny

    Did they do it with an iPhone?

  3. Let me guess by yabos · · Score: 4, Funny

    They used the transporter and the pattern from when the person beamed down on the away mission...

  4. Slight Clarification by eldavojohn · · Score: 5, Interesting

    I read about this in PhysOrg 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.

    --
    My work here is dung.
    1. Re:Slight Clarification by asliarun · · Score: 4, Interesting

      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.

  5. Seems like cheating by Mr.+Underbridge · · Score: 4, Interesting

    ...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.

    1. Re:Seems like cheating by JimbleBimble · · Score: 5, Informative

      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.

    2. Re:Seems like cheating by Otter · · Score: 4, Informative

      Here's the paper. I'm not a cell biologist, but from my limited understanding you're exactly correct.

  6. Proof of concept by PIPBoy3000 · · Score: 4, Interesting

    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.

    1. Re:Proof of concept by Mr.+Underbridge · · Score: 4, Interesting

      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.

  7. Re:Translation, please. by Sox2 · · Score: 5, Informative

    Cre is an bacterial enzyme (a member of a family of enzymes called site specific recombinases) commonly used by researchers attempting genetic manipulations of dna. The cre enzyme recgonises a specific dna sequence (called LoxP sites) just over 30 letters (base pair) long and then catalyses a reaction which can either cut out dna, insert dna or reverse the orientation of dna flanked by loxp sites (precisely what the cre enzyme will do depends upon the number of sites and the order and orientation of the sites). The HIV virus does not contain LoxP sites so these guys "evolved" the cre enzyme by a selective process to recognise DNA sequences that were initially a hybrid of a part of the HIV virus sequence and the cre Loxp site. they continues this evolution until a modified Cre enzyme (now called Tre) could actually recognise the original HIV dna sequence. They then used this Tre enzyme to cut out the HIV virus dna that had inserted itself into the cell genomic dna, freeing the cells of the HIV virus. This is a pretty interesting article, however, as the authors state this is preliminary work. One problem i can envision stems from the fact that HIV virus often inserts itself numerous times into the host genome. When researchers are using cre they have to be careful about the number of copies of the Loxp site in the genome or it is possible for the cre enzyme to cause large deletions of genomic dna or even cause translocations (when the genomic dna found on one chromosome is erroneously attached to that of another chromosome). Such changes to the dna can be highly deleterious to the cell and initiate cancerous changes. hope this helps.

  8. DNA Spoofing ? by Joebert · · Score: 4, Interesting

    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.

    --
    Wanna fight ? Bend over, stick your head up your ass, and fight for air.
  9. Re:In the shower.... by The-Ixian · · Score: 5, Interesting

    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.

    --
    My eyes reflect the stars and a smile lights up my face.
  10. Re:Translation, please. by m_frankie_h · · Score: 5, Funny

    Sure: Germans have created a variant of sed, that operates on DNA and used it to delete HIV.

  11. Re:In the shower.... by Anonymous Coward · · Score: 5, Funny

    Alright, I must be crazy. I was just thinking about HIV in the shower

    Are you currently serving time in prison by any chance?

  12. Re:Translation, please. by errxn · · Score: 5, Funny
    Sure, here ya go:

    "These German dudes ripped HIV out of your cells after it already got into your DNA. OMG! They think they might can cure AIDS with this. They're not too sure if it'll work, because it's gonna be WAY harder if you have AIDS real bad. 'The German dudes ... started out with this enzyme that'll swap out any DNA it finds that has these certain two nucleotide thingies on the ends of 'em with these mutant ones that they whipped up in the lab. Then this other one named Tre comes in, kicks ass, and takes names. After about 3 months, bye-bye, HIV! They were talking about it today in Science'"
    --
    In Soviet Russia, Chuck Norris will still kick your ass.
  13. Re:wild idea by StuckInSyrup · · Score: 4, Informative

    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.

    --
    Ni.
  14. Re:Translation, please. by mcrumiller · · Score: 4, Informative

    Sox2 explained it pretty well, I'll try to dumb it down even more. Certain enzymes recognize patterns on DNA, and chop them right at that location. HIV is a virus that inserts itself into your DNA (unlike most viruses, which just use your cells resources to reproduce). The scientists evolved an enzyme that recognizes the sites on either side of the HIV, chops them up, and splices them back together--effectively removing the HIV. The reason it's "preliminary work" and not a magical cure is because the 'patterns' recognized by the enzymes (and the enzymes themselves) were morphed into "fake" sites. In actuality, it's much harder to create enzymes that recognize the actual patterns of the HIV. In addition, these enzymes might find patterns elsewhere in DNA and accidentally chop up your DNA in the wrong locations, removing important parts of your DNA.

  15. Re:Translation, please. by eln · · Score: 4, Funny

    Well then all we need to do is write a simple script to iterate over all of the cells in the body and run the sed command. The list may be too long though, so we might have to use xargs, but that's no big deal.

    I always knew shell scripting would save lives one day.