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Doctors Will Test Gene Editing On HIV Patients 263

Soychemist writes "Some people have a mutation that makes them highly resistant to HIV, and scientists think that they can give that immunity to anyone with a new type of gene therapy. The first human trials will start at the University of Pennsylvania this week. Researchers will draw blood from people with drug-resistant HIV, clip the CCR5 gene out of their T-cells with a nuclease enzyme, grow the modified cells in a dish, and then return 10 billion of them to the patient's bloodstream. Those cells will be immune to the virus, and they will keep the patient's T-cell count up even if the rest are destroyed. 'We will see if it is safe and if those cells inhibit HIV replication in vivo,' said the lead researcher. 'We know they do in the test tube.'"
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Doctors Will Test Gene Editing On HIV Patients

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  • by dunezone ( 899268 ) on Wednesday February 04, 2009 @12:47AM (#26721223) Journal
    Every time someone posts about HIV we get a jackass like you. There are people who have HIV and didnt contract it through sex or drugs.

    There are people who were born HIV+ because their mother was a carrier, there are people who have been raped and now carry the virus, there are people in the medical field that contract it because some drug addict freaks out while they tend to them. Hell, even though we test blood now many people contracted it through blood transfusions before they tested it.

    Oh and by the way. Condoms don't give 100% protection against HIV its about 80-85%.

    HIV is a bastard of a virus. Our immune systems can usually handle most viruses without intervention. You cant win on your own against HIV. It will destroy the immune system eventually.

    If this treatment is successful at this level. At least we can give life to those who didn't have the choice.
  • by Mauzl ( 1312177 ) on Wednesday February 04, 2009 @12:48AM (#26721229)
    If you RTFA, its people who have drug-resistant HIV who are being experimented on.
  • by LonghornXtreme ( 954562 ) on Wednesday February 04, 2009 @12:56AM (#26721259)

    The test subjects have drug resistant HIV.

  • by LonghornXtreme ( 954562 ) on Wednesday February 04, 2009 @01:13AM (#26721341)

    There are 3 big risks / problems I see with this approach:

    #1: The modified T-Cells attack the host after they are reintroduced. Think of it like auto-immune disease or transplanted-organ rejection. This could cause effects ranging from a mild food allergy to death. Anyone know how much damage 10 billion rogue T-cells could do? I sure don't; however, I do know that they aren't a straight 1 T-Cell used up for each 1 antigen.

    #2: Unmodified T-cells attack the modified T-Cells because the surface of the modified T-Cells (i.e. the CCR5 protein) could possibly trigger an immune response. This would render the modified T-Cells kind of pointless. Seems like this would have better chance of working on patients with full blown AIDS rather than merely HIV+.

    3: Modified T-Cells survive and are unaffected by HIV; however, these surviving modified T-Cells are just clones of the one original T-Cell that the lab modified. So in essence, you have injected the test subject with 10 billion of the same T-Cell. Unless the doctors have a way of massaging the genes on a representative sample of T-Cells, then this is kind of useless to the patient. What good are 10 billion T-Cells if they are each only good for tagging one antigen? Meaning, that the 10 billion T cells could only respond to a single stimulus, i.e. they could all only fight one strain of the common cold, but not anything else.

    Disclaimer: I have a BA in bio from a public ivy; however, my GPA wasn't that great, and I didn't pursue a career in the field. I very well could be overlooking something substantial in immunology etc.

  • Unanswered questions (Score:3, Informative)

    by Michael Woodhams ( 112247 ) on Wednesday February 04, 2009 @01:26AM (#26721407) Journal

    Alas, I have enough biology to have questions not answered in the short article, but not enough to extract the answers from the referenced paper. (I did notice that the news article was slightly incorrect on one point. They are not actually 'clipping out' the CCR5 gene. They cause a break in the gene which gets imperfectly repaired, so that the gene becomes nonfunctional.)

    Are these T cells capable of 'reproducing' and having an unlimited number of descendants? This is not the case for many types of cells - it is part of what makes stem cells special. The paper refers to T4 cell lines, which suggests that they can indefinitely reproduce.

    If the treatment works, how long will it last? (If the answer to the previous question is 'no', the answer to this one will likely be be 'about as long as the lifetime of a T cell.' If the answer to the previous question is 'yes', the answer might be 'for a lifetime.'

    Do the modified T cells have to come from the patient? If not, the treatment will be much cheaper: Do the extraction and genetic modification once, breed up a big batch, treat dozens of patients. If not, you need to do the genetic modification once for each patient.

    Once you have a bunch of immune T cells, will they be able to eliminate HIV from the body? (I suspect not: I understand that as a retrovirus, HIV is very good at hiding dormant for a long while.)

    The answers to these questions are the difference between this being a laboratory curiosity and this being the elimination of HIV in developed countries within 5 years.

  • Re:bravo (Score:5, Informative)

    by Anonymous Coward on Wednesday February 04, 2009 @01:28AM (#26721421)

    Actually, this is far from the truth. I am an HIV-positive individual and based on the fact that my HIV was detected early and also that I started on HIV medications within the first year of contracting it my lifespan has been extended to the point where I will most likely live a full life. Before contracting HIV I thought it was a terrible thing to have and that I would kill myself if I ever got it. I have news for you: it is a terrible thing, but just like everything else in the world you get over it and with HIV medications having nearly NO side effects and once-to-twice daily dosing it makes life worth living.

    While some may speculate on whether or not I really know what I'm talking about, I do. I am a healthcare professional. For those of you who are wondering why I didn't post this under my account, I would rather not taint Google's results with gossip for my next employer. :)

  • by powerspike ( 729889 ) on Wednesday February 04, 2009 @01:32AM (#26721449)
    This isn't a drug, they are modifying the cells in such a way that the virus can't attach to them. Drugs genneraly add items into a body to counter an item, this is modifying the immune system directly itself, something that hasn't be done before. the CCR5 gene apparently is why around 50-60% of the English population survived the black plague in the dark ages, when the mortally rate in people without it is over 95%.

    There are a lot of deadly viruses that could be cured by this.
  • by 10101001 10101001 ( 732688 ) on Wednesday February 04, 2009 @01:39AM (#26721475) Journal

    It sounds like what they're thinking of doing is more like: (1) draw up 10 billion T-Cells, (2) use an enzyme to cleave off the CCR5 proteins, (3) filter out the enzyme+proteins, and (4) reinject the T-Cells. Ie, I don't think issue 3 would crop up (or, at least, it'd be much more limited in scope). The real issue, as I see it, is that those 10 billion T-Cells will eventually die. Not knowing enough about how proteins on the cell membrane are created/carried over during mitosis, it'd seem the biggest issue is that those 10 billion T-Cells are likely to either duplicate and regenerate the CCR5 protein or simply die out before the HIV is eliminated. Either situation would seem to only delay the spreading of HIV in the body.

    On the other hand, if it happens that the CCR5 protein isn't regenerated, then perhaps HIV would be cured, but you'd be at risk of redevelopment a random assortment of childhood illnesses (which should just mean revaccination). Unfortunately, I don't know nearly enough about T-Cell reproduction and HIV to know exactly how it is HIV manages to permanently kill off T-Cell production.

  • by MoellerPlesset2 ( 1419023 ) on Wednesday February 04, 2009 @01:41AM (#26721491)
    Not that I'm an immunologist, but:

    Are these T cells capable of 'reproducing' and having an unlimited number of descendants?

    T cells are produced by the bone marrow. They don't reproduce on their own.

    If the treatment works, how long will it last?

    The lifespan of an average T cell is on the order of 10-20 weeks. I believe. Shorter in HIV patients.

    Do the modified T cells have to come from the patient?

    Who knows? But not necessarily. After all, you get plenty of foreign T-cells with a blood transfusion. But I don't think anyone is necessarily viewing this treatment as a 'cure' in itself.

    Once you have a bunch of immune T cells, will they be able to eliminate HIV from the body?

    That's not known. But they've done it [], with positive effects. Note how 'cure' is put in quotes, as it should be.

    The answers to these questions are the difference between this being a laboratory curiosity and this being the elimination of HIV in developed countries within 5 years.

    That is ridiculous. It's neither.

  • Re:CANCER (Score:5, Informative)

    by Wain13001 ( 1119071 ) on Wednesday February 04, 2009 @02:04AM (#26721585)

    For the most part, T-cells die off naturally.
    People infected with HIV do not have to deal with a problem of too many t-cells, so in this case it's not much of a concern.

    Most importantly though, T-cells do not replicate to create more T-cells. They come from a type of lymphocyte starter cell (a stem cell essentially), which reproduces in the bone marrow.

    Taking t-cells from your body, and then reintroducing them to your body will not give you leukemia (literally meaning "White Blood", refers to various cancers of white blood cells).

    More than likely this is just a test, not *the cure*. The point being to see if the modified t-cells survive long enough to keep the count from dropping (as it would via a normal HIV infection). If it does work, then we can start developing methods to modify bone-marrow in order to make the new t-cells your body creates have the altered gene.

    Of course, I'm not an expert, and the article is unfortunately slim on details, so this is basic speculation.

  • by beav007 ( 746004 ) on Wednesday February 04, 2009 @02:11AM (#26721617) Journal
    Not to be a wet blanket for your argument, but this is being tried on drug-resistant HIV patients.
  • by sokoban ( 142301 ) on Wednesday February 04, 2009 @02:34AM (#26721743) Homepage

    I don't think 1 will be a problem. All T Cells have a CCR5 membrane protein, but the HIV resistant ones have a mutant type CCR5 protein. CCR5 is the way in which T cells get infected by HIV, and people with mutant type CCR5 genes survive quite well.

    2 may be a problem, and I think will be the biggest hurdle here.

    3 Shouldn't be a problem. Zinc Finger nucleases are able to delete the genes from a bunch of different cells at once. The idea is that you get a whole lot of T-Cells, Remove the 32 base pair segment from the two copies of the CCR5 gene in each T-Cell using zinc finger nucleases to make them the HIV resistant mutant type, culture more T-Cells which should be HIV resistant since they have the mutant gene, and inject the T-cells back into the patient.

  • by Anonymous Coward on Wednesday February 04, 2009 @05:35AM (#26722669)
    They have drug resistant HIV: they're aren't taking a cocktail, as it doesn't work.
  • CCR5 **delta 32** (Score:3, Informative)

    by CarpetShark ( 865376 ) on Wednesday February 04, 2009 @06:49AM (#26723001)

    They are not actually 'clipping out' the CCR5 gene. They cause a break in the gene which gets imperfectly repaired, so that the gene becomes nonfunctional.

    Indeed. They seem to be trying to modify CCR5 to be CCR5 delta 32, which is the variant which is less prone to HIV (but not immune). The nonfunctional aspect is very important, as you wouldn't want to simply engineer a foetus to have this gene instead of normal CCR5 genes. From wikipedia:

    The [CCR5 delta 32] allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV. Yersinia pestis was demonstrated in the laboratory to not associate with CCR5. Individuals with the d32 allele of CCR5 are healthy, suggesting that CCR5 is largely dispensable. However, CCR5 apparently plays a role in mediating resistance to West Nile virus infection in humans, as CCR5-d32 individuals have shown to be disproportionately at higher risk of West Nile virus in studies

  • Re:confused (Score:3, Informative)

    by CarpetShark ( 865376 ) on Wednesday February 04, 2009 @06:51AM (#26723017)
    Because it's a faulty/mutated gene, and not an alien organism, I imagine. I could (very easily) be wrong, but presumably the immune system doesn't deal with differences on that scale, unless they cause abnormalities further up the scale in the cell or something.
  • by fprintf ( 82740 ) on Wednesday February 04, 2009 @09:05AM (#26723637) Journal

    There are lots of engineers involved. My father ran a small medical startup some years ago and they made a very high tech (for the time) artificial ventilator that used rapid pulses of air rather than the typical high pressure slow pulses. They did lots of experiments on animals and had to jump through all kinds of hoops with the FDA just to be allowed to put the ventilator on a human subject. Essentially the only way, after the animal trials, to get the ventilator on a human patient was for the patient to be unresponsive to conventional treatment, at significant risk of death without intervention, and received signed autorization from the patient or guardian. (get those living wills drawn up and signed if you haven't already!)

    It took years, huge personal and venture capital investment, and eventually the company was bought out and I think the techology disappeared or otherwise got incorporated into standard ventilators. I posted this to illustrate all the work that needs to go into a medical device before it is allowed to be tried on humans... and even then, promising, even successful technology does not always make it in the marketplace. Believe it or not, Doctors are some of the *worst* luddites around and it is incredibly difficult to get enough momentum for a new technology to take hold.

  • by stranger_to_himself ( 1132241 ) on Wednesday February 04, 2009 @09:47AM (#26723959) Journal

    You could be worse off, as the study may require that you go off the regular HIV cocktail you are taking to suppress it.

    They would find it hard if not impossible to get ethical approval for that kind of study. If an effective treatment exists, controlled trials are controlled against that, and not against a placebo.

  • by Muad'Dave ( 255648 ) on Wednesday February 04, 2009 @10:06AM (#26724093) Homepage
    Ditto for Claritin and Clarinex. Loratadine vs Desloratadine.
  • by Muad'Dave ( 255648 ) on Wednesday February 04, 2009 @10:14AM (#26724175) Homepage
    The article said that this first test was to see if the new T-cells would live and if there would be any effect on the HIV load. This isn't the cure, only a step in that direction.
  • Re:Mutations (Score:3, Informative)

    by smellsofbikes ( 890263 ) on Wednesday February 04, 2009 @12:28PM (#26726243) Journal

    >What's to keep the virus from mutating and avoiding the CCR5 requirement it currently has?

    The virus uses the CCR5 receptor as its binding and entry point into the cell []. There are other receptors it might/may use, but CCR5 is the predominant one, especially early in the infection. As such, it's the gateway: if you can block it, that massively reduces the viral effectiveness.
    The process of developing a treatment for a disease is finding something the disease absolutely needs and targeting that. This is very difficult with HIV because, as you say, it has a high rate of mutation, but (as the wikipedia article says) at least in lab tests if you block CCR5, HIV infection drops by orders of magnitude -- so apparently, finding another route of entry is sufficiently complicated that it's highly unlikely that an otherwise viable mutation will evade this requirement.

  • And it begins... (Score:2, Informative)

    by jjrff ( 891275 ) on Wednesday February 04, 2009 @01:39PM (#26727169) Homepage
    the problem with that of course is it the basis for many a scifi movie; direct genetic manipulation resulting in a number of box office scenarios: - mass death (pick one...) - zombies (Resident Evil - the t-cell accident; was supposed to be a cure) - intentional mutation (Xmen 2 - the guy that made wolverine) - super soldiers (Super Soldier - the movies part 1 and 2, captain america) - Battlestar galactica (skin jobs and pro-creation attempts) - mutegenics wars - lots of super soldiers (Star Trek - not to be confused with Khan who is a eugenic offspring) - replicants (Blade Runner - note the replicants learned how to do this themselves...) - serenity (reavers were gene mutated - with the best of intentions of course) - I am Legend (someone else mentioned it already) I am sure the list goes on.
  • by Gizzmonic ( 412910 ) on Wednesday February 04, 2009 @03:57PM (#26728927) Homepage Journal

    If you understood anything at all about the HIV virus you would not promulgate this insipid argument. HIV is a retrovirus-it writes itself into your DNA, and you can't truly get rid of it (at least, not with today's technology). Don't let reality get in the way of your paranoid conspiracy theories.

Nondeterminism means never having to say you are wrong.