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Biotech Medicine

Researchers Modify T-Cells, Make Them HIV Resistant 171

DieNadel writes to share that naturally occurring proteins called "zinc fingers" are being used in a new approach to AIDS treatment. Using modified T-Cells with the zinc fingers, researchers at the Pennsylvania School of Medicine have shown a reduction in viral load in mice. "'By inducing mutations in the CCR5 gene using zinc finger proteins, we've reduced the expression of CCR5 surface proteins on T cells, which is necessary for the AIDS virus to enter these immune system cells,' explains first author Elena Perez, MD, PhD, Assistant Professor of Pediatrics at Penn. 'This approach stops the AIDS virus from entering the T cells because it now has an introduced error into the CCR5 gene.'"
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Researchers Modify T-Cells, Make Them HIV Resistant

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  • by nekdut ( 74793 ) on Wednesday July 02, 2008 @05:30PM (#24036617) Journal

    Aren't we having a zinc shortage []? Get it from these fingers!!

  • OMGZombies! (Score:5, Funny)

    by gorckat ( 960852 ) on Wednesday July 02, 2008 @05:32PM (#24036641)
    Oh wait...T-cells. I thought it said T-Virus.
  • by conspirator57 ( 1123519 ) on Wednesday July 02, 2008 @05:40PM (#24036723)

    what *else* do these surface proteins on the T cell do?

    maybe there is something those altered structures do that we will miss when they stop performing their function...

    not everything in the body is superfluous like the appendix or wisdom teeth.

    • by troybob ( 1178331 ) on Wednesday July 02, 2008 @05:46PM (#24036805)
      OMG you had better try to get in touch with these researchers, because this probably did not occur to them at all!
    • by nizo ( 81281 ) *

      Considering AIDS eventually leads to painful death, what function would this hinder that would make things worse?

      • by DarkOx ( 621550 ) on Wednesday July 02, 2008 @07:30PM (#24037941) Journal

        Well, I am no AIDS expert but from what I understand is HIV does not really kill anybody. AIDS the resulting condition of HIV, is Auto Immune Difficency Sydrome. Basically you immune system stops working and all the other little virus out there take over start to take over all your other cells and with nothing to stop them; that kills you.

        So if you screw-up someones immune system in the name of HIV proofing and that causes it to not work then they will have AIDS anyway even if you do manage to kill off the HIV infection. So yea if it turns out these things are "important" you might destroy the immune system faster then HIV would have.

        • I have always loved that explanation. The first thing that came to my mind when I first heard it, was that falling does not kill you, no matter how far, only the sudden stop at the bottom.


          • Rincewind: I'm not going to ride on a magic carpet! I'm afraid of grounds.
            Conina: You mean heights. And stop being silly.
            Rincewind: I know what I mean! It's the grounds that kill you!

        • AIDS stands for Acquired Immunodeficiency Syndrome, not Auto-immune. It's an infectious disease, not a manifestation of lupus or rheumatoid arthritis.

        • by Guppy06 ( 410832 )

          "Well, I am no AIDS expert but from what I understand is HIV does not really kill anybody."

          "Guns don't kill people..."

        • ... HIV does not really kill anybody ...

          Actually, it does, it's just most people die of AIDS before the HIV infection itself can kill. In addition to infecting immune system cells, HIV also infects brain cells, which is the cause of the cognitive impairment descending into dementia that is experienced by a significant number of late-stage AIDS patients. If the patient doesn't die of infection first, AIDS dementia complex [] can destroy enough brain tissue to finish them off.

    • by Gat0r30y ( 957941 ) on Wednesday July 02, 2008 @06:01PM (#24036985) Homepage Journal
      FTFA -

      Some people are born with a mutation on their CCR5 gene and therefore do not have a working CCR5 receptor on the surface of their T cells. These rare individuals are immune to HIV infection and seemingly are not affected by the non-functional CCR5 protein. The zinc finger approach aims to mimic this natural immunity.

      It would appear that these surface proteins are "superfluous", or at least not really necessary.

    • by wizardforce ( 1005805 ) on Wednesday July 02, 2008 @06:07PM (#24037073) Journal
      whatever function they have, it's probably not as important as not dying of AIDS
      • Re: (Score:3, Interesting)

        by PCM2 ( 4486 )

        whatever function they have, it's probably not as important as not dying of AIDS

        Upon what data do you base that assumption? Is not dying of AIDS more important than not dying in screaming agony? []

        • Re: (Score:3, Insightful)

          Upon what data do you base that assumption?

          considering the kind of death that is in store for someone who is severely immuno-compromised, the adverse effects from this treatment would need to be pretty bad to be considered worse. that and there isn't any convincing evidence to my knowledge that this method is any worse than doing nothing to mitigate the effects of an HIV infection which doesn't mean that there can't be any that we don't know about, it means that we would need more testing- in any case, di

        • So you're saying that people with AIDS don't suffer horrible agonizing death from various infectious diseases?

    • by Andy Dodd ( 701 )

      Well it would probably be a bad idea to do this pre-emptively prior to an HIV infection, but once someone was infected - If it's a choice between "dead T-cells/no T-cells" and "potentially malfunctioning T-cells", "potentially malfunctioning" is better than "none/dead".

  • by geekmansworld ( 950281 ) on Wednesday July 02, 2008 @05:40PM (#24036727) Homepage

    Haven't we learned not to modify T-Cells already?

  • Thats sick (Score:3, Funny)

    by Gat0r30y ( 957941 ) on Wednesday July 02, 2008 @05:43PM (#24036761) Homepage Journal
    sorry. I had to.
  • by Whuffo ( 1043790 ) on Wednesday July 02, 2008 @05:45PM (#24036793) Homepage Journal
    HIV is a polymorphic virus - it changes its "shape" often, making vaccines difficult / impossible to create. Sure, they can create a vaccine for variation 32b, but there's a bunch of variants and new ones show up from time to time. A nice simple AIDS vaccine that you can give to kids is - as far as we know at this time - impossible.

    But this technology may provide a way to defend against this virus. By changing the "shape" of our T-cells it will prevent the virus from recognizing its target. This would render it ineffective and be effective against the numerous variants.

    Of course, this is still early in the development cycle. There's always the chance of unintended consequences...

    • by Red Flayer ( 890720 ) on Wednesday July 02, 2008 @06:02PM (#24036989) Journal

      But this technology may provide a way to defend against this virus. By changing the "shape" of our T-cells it will prevent the virus from recognizing its target. This would render it ineffective and be effective against the numerous variants

      This does not make the T-cell invisible to HIV, it sets a trap.

      T Cell (in sexy voice): How about it, Mr. HIV, do you want to come into my place?
      HIV: Om nom nom let me put my arms around you baby... wait, where the fuck do I put my left arm? I can't penetrate without both arms around you!
      T cell: All your binding proteins are belong to me.
      HIV: I'm going to go hit on someone else. Let go of my right arm, you bastard!
      T cell: Om nom nom

      Well ok, it's a stretch, the T cell doesn't eat the virus at the end.

      But the zinc fingers don't disguise the T-cell, they keep the T-cell from expressing one of the antigens on its surface. So instead of the two binding sites needed for the T-cell to be infected, it only shows one.

      • I find your dating example pretty ackward,
        I've never seen a sexy T-cell before but anyways...

      • by GroeFaZ ( 850443 ) on Wednesday July 02, 2008 @06:39PM (#24037441)
        Couldn't you have put it as an analogy that does not involve "making out"? Something slashdotters can understand, like, a car analogy?
      • Perhaps I am simply ignorant, but is it impossible that mutations in the AIDS virus could adapt to this? Also, how can one change the genetic code in all of the existing cells in the body to produce only the new and improved T-Cells and even if we could do that what other side effects might that have? I seem to remember from a couple of articles that attempts to alter genetic code of living humans (through viruses for example) has had limited success and resulted in death of the patient in some cases. I sup
        • Retroviruses do this DNA-mutation on the fly all the time.

          That's why they end up as part of our lineage's DNA.

          • HIV viruses might work

            • Actually, that's kind of the weird thing about HIV. It infects its host, then the host "wins", and the HIV is almost unnoticeable at that point. However, enough T-cells have the odd DNA code that HIV inserted into it, and so far, I've only heard it as "mysteriously" the T-cell levels drop, even though the virus is in remission. The virus eventually takes over, because the T-cells aren't in high enough numbers to stop it anymore, but the T-cell levels drop WHILE they're winning against HIV.

              I can only thin

        • Re: (Score:3, Informative)

          by Red Flayer ( 890720 )
          It's not possible* for the HIV virus to adapt to this, as it requires two different binding sites. If you remove one of the sites, binding and insertion is impossible.

          As for changing the genetic code, that's not what you're doing. Instead you are putting out a honeypot to attract the virus. The virus can still infect normal cells, but the modified cells can't be infected -- if you have enough of them, then the normal cells can go about their business. Here's a very simplified model:

          Say each generation
          • You can practically get rid of the virus over many successive generations.

            but never entirely right? This sounds similar to HAART, it can reduce the virus to very low levels, but it would take more than a normal human lifetime to clear the virus completely using these types of methods. At best it would probably allow a reasonably normal, if somewhat shortened, lifespan with the virus never completely cleared but (hopefully) well controlled.

      • This is /. Did you really think anyone would really get the dating analogy?

        Next time, use a car analogy, please.

      • by Barny ( 103770 )

        So, to put it in a way people on here might actually understand ;)

        The T-cell fakes its md5, HIV comes up, checks to see if this is the right cell to corrupt and finds the hash doesn't match what it wants, and ignores it.

        See, and no cars or tubes :)

    • How about a virus that binds only to cells that express both the T-cell receptor and whatever HIV uses to connect to the T-cell receptor? Presumably, only infected cells would express both - the former because that's how HIV got in there, and the latter because HIV is being produced and HIV itself uses the cell's surface as a coat when budding.

      Now, HIV may mutate so that the virus wouldn't recognize the "T-cell inverse", but there's a limit to how much it can mutate before the receptor fails to connect t
    • by Cyberax ( 705495 )

      I'm skeptical.

      HIV is known to evolve affinity for new binding sites: []

      Can it evolve around this change? I don't know, but it's very probable.

  • by JDevers ( 83155 ) on Wednesday July 02, 2008 @05:49PM (#24036829)

    Talk about completely misreading even the one paragraph blurb. Zinc fingers are a large group of protein sub-structures which are used to interact with DNA. This group used them to induce a specific mutation which now seems to be HIV resistant How long this will last is really up in the air though, HIV and all other RNA viruses evolve very quickly.

    • by Otter ( 3800 )
      In fairness, the blurb here comes straight from the godawful UPenn press release, which refers to "minute, naturally occurring proteins called zinc fingers". The "minute" is also odd.

      How long this will last is really up in the air though, HIV and all other RNA viruses evolve very quickly.

      That doesn't seem to be a problem with the naturally-occurring CCR5 variant, though.

      • by JDevers ( 83155 )

        The naturally occurring variant is such a small percent of the population as to not be an evolutionary pressure for HIV, if huge numbers of people all of a sudden basically have this gene that pressure will increase quite a bit.

  • Who wrote that summary? They can't even get the name of the school right - it's the University of Pennsylvania School of Medicine.

    Man, them's some shitty editorial standards you've got there.

  • Anyone else read this as a CRC error?

  • by my_left_nut ( 1161359 ) on Wednesday July 02, 2008 @05:54PM (#24036905)
    "Researchers Throw Finger at HIV"
  • Brilliant! (Score:5, Funny)

    by DeVilla ( 4563 ) on Wednesday July 02, 2008 @06:06PM (#24037063)
    That sounds like a great plan. Insert errors into our genetic code until the virus leaves us alone. That's got to work.
    • That sounds like a great plan. Insert errors into our genetic code until the virus leaves us alone. That's got to work.

      Well, one in every billion-odd genetic errors results in evolutionary mutation. I suppose if you're feeling really lucky...

      (Hey, they got us this far!)

    • If only the same principle worked for Microsoft...
    • Ummm, you do realize that that's how evolution works, right? Any mutation (beneficial or not) can be seen as a "random error".

    • As it happens errors in the CCR5 receptor occur naturally and with a significant frequency, mainly in European populations. This 'delta32' mutation results in a defective receptor, but the people with it are healthy. There is also a drugs on the market, maraviroc, that specifically inhibits CCR5. People with the CCR5-Delta32 mutation are 'long term non progressors', they carry the virus but don't develop AIDS, probably because the virus is incapable of destroying their immune system. HIV is actually found
  • For years I've heard of HIV research focusing on either slowing the spread of HIV or focusing on killing the virus.

    This solution instead makes it so the virus will have no effect. I would imagine that a HIV infected victim that has not been vacinated should even be able to receive immunized T-cell injections or even pill supplements.

    The approach to this problem just reminds me of the kid that suggested letting the air out of the tires of the bus stuck in the tunnel. Of course it's obviously much more techni

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