HIV-immune Cells

  by  |  August 22nd, 2008  |  Published in All, Animals & Life Science, Health

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Doctors are considering using a new technology to genetically modify AIDS patients’ own cells to be resistant to HIV. As this ScienCentral News video explains, they’re modeling the idea after rare individuals who are naturally immune to the AIDS virus.

[If you cannot see the You Tube video below, you can click here for a high quality mp4 video.]

Interviewee: Dr. Carl June, University of Pennsylvania
Produced by Joyce Gramza — Edited by James Eagan
Copyright © ScienCentral, Inc., with additional footage courtesy of
the Centers for Disease Control and Sangamo Biosciences.

Natural Resistance
by Caroline Parnass

Before there was a way to screen donated blood for HIV, many people were exposed to the deadly virus through blood transfusions. But some rare individuals who received infected blood or other HIV exposures never developed AIDS.

When HIV manifests itself in the form of the disease AIDS, or acquired immune deficiency syndrome, the viruses attack the patient’s immune system, killing off the cells that fight infection. This is why most AIDS patients die from opportunistic infections, or infections that people don’t normally get unless they’re immunologically compromised, such as pneumonia or Kaposi’s sarcoma.

Over years of intensive study, scientists have discovered that an exceedingly small number of people have a natural immunity to HIV due to a single genetic mutation called delta 32, a deletion of 32 letters of DNA on the CCR5 gene, which codes for a molecule that HIV uses to enter immune system cells. This molecule is analogous to the cell’s gatekeeper, allowing things in and out of the cell; if it’s not there, the HIV cannot infiltrate the cell.

“In fact, this resistance is so robust that they can be exposed multiple times, even through blood transfusions from people who have HIV, and they don’t get infected,” says Carl June, professor at the University of Pennsylvania School of Medicine, and Director of Translational Research at the Abramson Family Cancer Research Institute.

Mimicking Mother Nature

Now researchers led by June are testing a new way to create that same natural immunity in people who already have HIV, and as they recently announced in the journal Nature Biotechnology, they have had encouraging success working with mice. “What our work did,” says June “was to find a way to disable this gatekeeper in a way similar to people who are born, those fortunate few, who have a natural immunity to the virus.”

June, along with Elena Perez, now at Children’s Hospital of Philadelphia, worked with other colleagues on a very powerful type of gene modification that uses zinc finger proteins or “ZFPs.” ZFPs are modeled after naturally occurring proteins that act as transcription factors, telling the cell which genes should be expressed and which should not. Co-author Philip Gregory, Vice President of Research at Sangamo Biosciences, where the technique for designing specific ZFPs was invented, says that with these proteins, “we’re able to switch on or switch off the expression of essentially any gene in the human genome.”

“A zinc finger nuclease can be designed so that it will find literally a needle in a haystack, one gene out of 30,000,” says June. The researchers had to test hundreds of ZFPs to identify one that could find and break the CCR5 gene, and prevent cells from producing the HIV gatekeeper molecule.

They then tested the modified cells in mice exposed to HIV, and observed that the mice that received the modified cells maintained normal immune systems, and had lower levels of the virus in their bloodstreams.

Hope for a New Treatment?

“This is the first time you could induce a permanent resistance of cells to the HIV virus,” says June. “The way we would normally do this is we would have to treat animals or people every day with medications. And this is a permanent treatment where, after this one time, the introduction of cells that have this HIV gatekeeper were able to fight off the virus. The other problem with the current therapies is that there are side effects,” notes June, “and those side effects are sometimes so severe that the patients have to stop taking medication, and then those patients really have no alternative.”

HIV has shown time and again that it’s good at mutating and thwarting treatments. But since this strategy shuts the door on the virus, the researchers are hopeful it may have an advantage there as well.

“This is the earliest stage of HIV infection,” says Gregory. “It’s the block to HIV entry into the cells it would normally enter.”

“Hit and Run”

Gregory explains that while the HIV treatment uses a viral vector to deliver the ZFP into cells, it’s not gene therapy in the traditional sense, because gene therapy relies on integrating foreign material into cells. “It’s like you put the virus in and it goes into the cell’s DNA and it stays there,” he says. Using viruses that integrate into genes has caused some major safety issues, even in successful gene therapy, he points out.

“We’re actually using a viral vector based on a common cold virus, called the adenovirus,” Gregory says. “The reason we chose it is that, other than having a viral coat on the outside, it’s a vector that does not integrate into the genome, so it’s rarely used in gene therapy applications these days because it only provides such a transient delivery mode. But in our case because we only need a transient delivery mode, it has the right characteristics for us.”

The researchers call this approach “hit and run,” and Gregory points out that the ZFPs are given to donated cells “ex vivo,” or outside the body. “The ZFPs are introduced, they carry out this genetic change, it’s permanent, but the carrier… the vector that gets the ZFPs into the cell, and the ZFPs themselves are washed out. And so what goes back into the patient is a modified cell that doesn’t have either the vector or the ZFP’s in it anymore.”

The research team is now planning safety tests for the treatment in HIV patients, using their own modified cells. June says in the short-term, they’ll start with small doses of modified cells and follow patients closely to monitor safety, and to see whether the cells are in fact exhibiting HIV resistance.

“In the long term, if this passes the first safety hurdles, we’ll then test the safety of giving multiple blood transfusions of immune cells,” June says “And if we can find that that approach is safe as well, then the next step would be to do this in their bone marrow cells so that the whole body would then become repopulated with cells that have natural resistance to HIV virus.”

This article was published in the July 29, 2008 edition of Nature Biotechnology, and the research was funded by the National Institutes of Health, NIST Advanced Technology Program, the Abramson Family Cancer Research Institute, Center for AIDS Research Cores and Sangamo Biosciences.

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  1. Loknar says:

    August 23rd, 2008 at 11:48 pm (#)

    Is this gene therapy safe for women wishing to be pregnant someday? If you think about it, this is a pertinent question…

  2. elena says:

    August 26th, 2008 at 1:18 am (#)

    When is this method is going to be acessible por everybody? If we want to try it, were can we do it?

  3. jake says:

    September 4th, 2008 at 7:05 pm (#)

    You're a total moron, you shouldn't be having children. Problem solved.

  4. jinga says:

    September 21st, 2008 at 4:02 pm (#)

    Advanced Alternative HIV Treatment Bio-Tech

    Planet earth is technologically advanced and developed more than ever before. Electricity, Nuclear, DNA, Electromagnetic Radiation, Oxygen is all being used to treat and cure several viral infections in hospitals and clinics but unfortunately none of such technologies have ever been widely used on HIV.

    Some say, the above technologies are too expensive to be adopted in Africa, some say they don’t know if the technology would work on HIV.

    Here at Savec Health Systems in Belfast UK headed by a HIV orphan medical engineer, we researched and developed alternative medicines commonly used for treatment of viral infections. One of our products is omnivir, a medical device that generates antiviral active oxygen, also known as medical ozone.

    HIV, just like any other retro-virus has a lipid protective skin which is vulnerable to active antiviral oxygen / medical ozone . Once the HIV protective skin is damaged, the virus will be inhibited and rendered unproductive thus it cant make more copies or replicate itself and it eventually dies.

    Active oxygen deactivates and eventually kills the HIV by destroying its protective skin. Using omnivir medicine properly will help to reduce the HIV viral load in the body, enabling the body to fight opportunistic infections on its own. Omnivir gas is quickly absorbed into the whole body and lymph, even into the bone marrow where it acts against the viruses. The active oxygen’s destructiveness nature on HIV, virus and bacteria is partly attributed to the oxidation (burning of viruses) of unsaturated bonds in the phospholipids and lipoprotein architecture of the bacteria, viruses. All viruses cant live in oxygen , (they breathe nitrogen) , thus surrounding them with highly active form of oxygen / medical ozone will quickly inactivate and kill them.
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    Omnivir treatment gas does not only kill HIV or opportunistic infections, but also helps to boost the immune systems by raising the CD4 count. The immune system contains different types of cells that help protect the body from infection. One of these types of specialized cells are called the CD4 or T-cells. HIV attacks these types of cells and uses them to make more copies / multiply. And in doing so, HIV weakens the immune system, making it unable to protect the body from illness and infection. The less the CD4 cell count the more you are susceptible to AIDS causing infections. Using omnivir will help you stay health and live a normal long life by killing the HIV and aiding reproduction of the CD4 T Cell.


  5. Joyce_Gramza says:

    September 22nd, 2008 at 1:05 pm (#)

    Hi all– Here's an email response to some of your questions from the researcher:

    1) Is this gene therapy safe for women wishing to be pregnant someday?
    you think about it, this is a pertinent question…
    Answer: The principal aim of our Phase 1 trial will be to test the
    safety of this procedure in subjects with HIV infections. However, we
    have tried to make this as safe as we can. The procedure is designed to
    disrupt the CCR5 gene in immune system cells from the blood that are
    taken from the subject and exposed to the ZFNs outside the body. Before
    being reinfused back into the subject the cells will be checked to
    ensure that only the intended changes have been made. At that point we
    also expect that the ZFNs will have been degraded and so they will not
    be introduced into the subject and should not have future consequences
    for the subject.

    2) When is this method is going to be acessible por everybody? If we
    want to
    try it, were can we do it?

    The first clinical trial of this therapeutic will be run by Dr. June and
    his colleagues at the University of Pennsylvania School of Medicine. We
    hope to get this into the clinic as soon as possible.


  6. aids drugs says:

    November 17th, 2008 at 7:36 pm (#)

    Gene therapy in women who want to have babies one day would simply mean they pass on this resistance, which could be seen as a very good thing. I think enhancing the bodies natural defenses is a really good route to follow in the fight against HIV.

  7. Edward Bass says:

    February 14th, 2009 at 4:42 am (#)

    Bone marrow transplants are extreamly life threatening in themselves and I could not see them as routine treatment for HIV even if this works.

  8. 細胞膜上爭千秋: 抗藥性與愛滋病免疫新聞兩則 - MMDays says:

    March 2nd, 2009 at 11:16 am (#)

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  9. Tristen says:

    April 21st, 2009 at 12:36 pm (#)

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  10. colon detox says:

    July 29th, 2009 at 12:42 am (#)

    i wonder when are we going to have the cure for HIV/AIDS ? we are living on an age with very high technology but still we have not found a cure for this disease.

  11. 細胞膜上爭千秋: 抗藥性與愛滋病免疫新聞兩則 says:

    August 5th, 2009 at 9:59 am (#)

    [...] (ScienceCentral) HIV-immune Cells [...]

  12. arthritishelp says:

    October 10th, 2009 at 1:49 am (#)

    HIV/AIDS is still rampant today and there is no cure for it. we need to practive safe sex all the time because an ounce of prevention is still better than a pound of cure.

  13. Marriane says:

    November 23rd, 2009 at 9:11 am (#)

    HIV/AIDS is still a problem today despite huge medical advances, i am wondering if there would ever be a cure for this disease .

  14. Ruby Hernandez says:

    November 26th, 2009 at 8:59 pm (#)

    it is just a matter of time for the cure to be finally found… at least our scientists are on the right way.

  15. Andre says:

    January 19th, 2010 at 5:35 am (#)

    I think this gene therapy will not affect women who wants to be pregnant as it is only supposed to mutate the T4 lymphocytes to get rid of the gateway… Which will then not allow HIV virus to release their DNA into the T4 lymphocytes to be infected.
    This is my opinion.

  16. Jake Cullen says:

    March 1st, 2010 at 6:27 am (#)

    HIV is a disease that is still incurable today. We should always practice safe sex and also educate our people how to avoid the spread of this disease.

  17. deeque says:

    April 29th, 2010 at 4:33 am (#)

    What is the progress on this study so far, people are dying as we speak

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    May 1st, 2010 at 3:02 am (#)

    The usual remedy for common cold is just lots of water, fruit juice and also vitamin-C tablets.*;*

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    August 12th, 2010 at 1:08 pm (#)

    you can actually shorten the symptoms of common cold by taking lots of vitamin-c,~’

  20. Celebrity Gossips Forum · says:

    November 8th, 2010 at 7:01 am (#)

    common cold is really hard to prevent becaue the virus always mutate ..

  21. davey says:

    November 27th, 2010 at 10:26 pm (#)

    it was in 1982, when the first of my friends was stricken down by this ugly didease. Here I sit, almost 30 years later, and the deaths of all of my friends, that I am bewildered at how I am still alive having escaped infection. And wondering if a cure will be found in my lifetime. I am abstinant, even if a vaccine is found, I sure the hell wont “press my luck”, I will abstain as if the disease were still a threat to anyones life!

  22. David Lo says:

    July 20th, 2011 at 7:13 am (#)

    We humans are not God. Gene therapy has been studied for how long? Any concrete results? HIV-1 vaccines seem to be big pie in the sky. We should conduct safe sex. Besides, we should emphasize on family life. Now it is almost four years from this news publicized. Any further progress?

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