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Medicine Science

Researchers Successfully Cut HIV DNA Out of Human Cells 64

Posted by Soulskill
from the uses-for-your-trusty-nanoknife dept.
mrspoonsi sends word that researchers from Temple University have managed to eliminate the HIV-1 virus from human cells for the first time. "When deployed, a combination of a DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and excise the HIV-1 DNA (abstract). From there, the cell's gene repair machinery takes over, soldering the loose ends of the genome back together – resulting in virus-free cells." While antiretroviral therapy can treat people who are infected with HIV, the immune system is incapable of actually removing the virus, so this is an important step in fighting it. The researchers still have to overcome the problem of delivering the the genetic "toolkit" to each affected cell in a patient's body, and also HIV's high mutation rate.
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Researchers Successfully Cut HIV DNA Out of Human Cells

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  • From TFA:
    "...soldering the loose ends of the genome back together..."

    I sure hope they used RoHS solder (aka sodder for the US people). Lead is toxic to cells.

    • (aka sodder for the US people)

      I'm from the US. I'm fluent in English. "Sodder" ain't real English.

      Trying to capture the phonetics of a local dialect when writing dialog is one thing, but it's an insult to others when you provide a dumbed down misspelling of a word and suggest that it's for their benefit. Besides which, the silent L is well-establish in both of our dialects (e.g. could, would, alms, calm, half, and folk all have silent Ls in accepted usage of either British or American English, though obviously there are non-standard pro

  • Delivery method (Score:4, Interesting)

    by Anonymous Coward on Tuesday July 22, 2014 @07:25PM (#47511551)

    "The researchers still have to overcome the problem of delivering the the genetic "toolkit" to each affected cell in a patient's body"

    Solution: Use the HIV virus itself

    http://www.scripps.edu/news/press/2014/20140626torbett.html

    "Viruses infect the body by inserting their own genetic material into human cells. In gene therapy, however, scientists have developed “gutted” viruses, such as the human immunodeficiency virus (HIV), to produce what are called “viral vectors.” Viral vectors carry therapeutic genes into cells without causing viral disease. Torbett and other scientists have shown that HIV vectors can deliver genes to blood stem cells."

    The irony in this solution would be over 9000.

    • by sg_oneill (159032)

      Actually a Judas-virus approach would be perfect since its already clear that the body seems unable or unwilling to kill the virus, its free to move into place to knife its buddies. And if the body does decide to start killing the viruses, well all the better really it means the body now realises HIV isn't something to keep about!

    • Its not so easy, viral vectors work well to deliver nucleic acid sequences to act directly or by the proteins that they encode.

      This approach unfortunately depends of the combination of a protein and a sequence of RNA, even if you can make a viral vector that encodes both the RNA sequence and the nuclease so they can be produced, there is no process that can be used to combine them both inside the cell, so they cannot function.

      A good delivering method effective for this kind of approach would also allow seve

    • by Kyrubas (991784)

      Yeah, so something like this:
      http://xkcd.com/938/ [xkcd.com]

    • by Mortiss (812218)

      Solution: Use the HIV virus itself

      A possible problem with that approach might be that on cell level, HIV posesses mechanisms such as CD4 downregulation (CD4 is HIV receptor) that are designed to prevent another HIV virus from further infecting already infected cells. This mechanism ensures that idividual cells don't get superinfected and don't die prematurely.

      Hence using modified HIV "viral vector" might not be the best option here, but there are lots of other virus vectors although getting them to exhibit exactly same tropism like HIV (

  • I'm astonished that they haven't made more progress on cancer. I know it's like comparing apples and oranges, and I realize that cancer is a whole bunch of diseases while HIV is a handful of strains of the same virus. Still, cancer research has been very heavily funded for far longer than HIV research. Yet it seems that very little progress has been made on cancer beyond 'cut it out, poison it, nuke it', while attempts at eliminating HIV seem more subtle and nuanced by comparison. I know I'm probably missin

    • Can you not see that this research is directly applicable? Arguably cancer can be considered a copy error (wouldn't it be nice if our DNA had CRC?) If you think about it like that it seems that you could replace the error bits in just this fashion, and voilla.. Cancers ( all of them, as well as a shitload of other genetic issues ) are a memory.. Now where the hell do we put all the people?
      • by miknix (1047580)

        The thing is that as horrible as it may sound, cancer is part of evolution. When there is a genetic mutation, there is high change it turns out into just cancer but it can also turn out into another eye color, or immunity against a virus. If you put a CRC into our genome, then we could never evolve genetically anymore. But then, well, some say our natural process of genetic evolution stopped the moment we learned to change the genome.

        • Exactly this.. If we can successfully place a CRC into our genome I posit that we are no longer in need of random mutation to guide our evolution.. I for one can think of a couple dozen genetic hacks I would give a lot for.
        • The normal evolutionary mutations happen only in (proto-)gamet cells. Cancer mutations happen mostly in non-gamet cells.

    • by structural_biologist (1122693) on Wednesday July 23, 2014 @12:02AM (#47513047)
      Here is probably the biggest difference in terms of a drug-development perspective: HIV relies on enzymes that are not normally found in the human body, so it is relatively easy to find drugs that can target these proteins without causing significant side effects. Cancer cells, however, are human cells themselves, so the proteins that drive tumor growth and malignancy are found in healthy cells as well. Thus, developing anti-cancer drugs is not just a matter of finding and inactivating the proteins that drive cancers, but also making sure that inactivating these targets does not harm other non-cancerous cells in the body.
    • by clawsoon (748629)
      Look into Gleevec and other tyrosine kinase inhibitors for examples of a few highly specific cancer treatments that we've managed to developed for a few of the "whole bunch of diseases" that cancer is.
  • a tiny step.. (Score:3, Informative)

    by Anonymous Coward on Wednesday July 23, 2014 @12:13AM (#47513089)

    http://www.pnas.org/content/early/2014/07/17/1405186111.abstract

    This isn't such a big deal. Cas9/CRISPR is being used for all sorts of applications. This is just one of them, and the actual challenge isn't editing the genome, it is delivering Cas9/CRISPR to all cells of the body and having them being specific. That is far, far more difficult.
    The authors detected INDELS (insertion/deletions) within the HIV-1 targetted sequence, so that is good -- it's doing what it should be in that respect.

    However, Cas9/CRISPR can go OT (off target) and edit non-targetted DNA. It is the most specific editing tool that anybody has ever found, and will no doubt be Nobel-Prize worthy one day. But if OT effects happen, this is bad, when you start deleting/editing bits of DNA randomly - things can go wrong, cells and tissues can do things they're not meant to. Although that is fairly rare with Cas9/CRISPR -- however when exposed to megabases of DNA even rare events can become frequent (I would consider 1 OT effect too many for me, if I was about to be injected with something that was going to edit my Genome).
    The authors did detect some OT effects (from their paper published in PNAS). So they carefully use the phrasing "minimize" OT effects in their paper. Also, they say "The long-term expression of Cas9/LTR-A/B gRNAs did not adversely affect cell growth or viability, suggesting a low occurrence of off-target interference with the host genome or Cas9-induced toxicity in this model." while it's a golf-clap worthy assay for cells in a dish (where's the rest of the assays for motility, cilial function, cell cycle length, etc.?), that isn't good enough either when uttering the words 'therapy'.

    It's kind of neat, but I can see why this is PNAS and not Nature or Nat Med.

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