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Molecular Scissors May Help Potentially Cure AIDS in the Future

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We will know in a few years if a new treatment will end up being a cure for AIDS.  This image of the AIDS quilt is courtesy of Wikimedia Commons.

We will know in a few years if a new treatment will end up being a cure for AIDS. This image of the AIDS quilt is courtesy of Wikimedia Commons.

Ever since AIDS emerged as a deadly disease in the early 1980’s, scientists have been looking for a cure. And now, using a very precise set of DNA scissors, they may finally be taking baby steps towards one.

The new hope rests on the old observation that a few people are highly resistant or even immune to HIV, the virus that causes AIDS. These people can live a high-risk lifestyle that results in multiple exposures to the virus and still never end up with the disease.

When scientists looked at these people’s DNA, they found that many of them shared a specific genetic mutation called CCR5 delta32. This mutation inactivates the CCR5 gene which means these people make no CCR5 protein. This lack of CCR5 protein makes these folks highly resistant to getting AIDS because the most virulent form of the virus, HIV-1, needs it to get into blood cells. No infection means no AIDS.

While this is interesting and obviously a boon to the small minority of people with this mutation, it doesn’t seem like it would be very useful for people already infected with HIV. And yet it has turned out to be incredibly useful.

Learning about this mutation pointed scientists towards a new class of drugs, CCR5 receptor antagonists. These drugs block the action of the CCR5 protein making it very difficult for HIV-1 to enter the patient’s blood cells. At least one of these, Selzentry, is currently being used to treat some cases of HIV.

And this isn’t even the most exciting use of this discovery. Scientists in Germany actually used this knowledge to cure a man of his AIDS!

The molecule in yellow, CCR5, may be the key to an eventual cure for AIDS.  Image courtesy of Wikimedia Commons.

The molecule in yellow, CCR5, may be the key to an eventual cure for AIDS. Image courtesy of Wikimedia Commons.

Back in 2007, an AIDS patient in Berlin Germany was told he would need a bone marrow transplant to treat his newly diagnosed leukemia. He and his doctor decided to seek out a donor who had the CCR5 delta 32 mutation. The hope was that this bone marrow transplant would treat both of his diseases at once. Their hope was realized: his leukemia went into remission and his viral load became undetectable. This bone marrow transplant cured his AIDS.

Bone marrow transplants replace a patient’s blood stem cells with the donor’s. What this means in this case is that the AIDS patient now had the donor’s blood cells coursing through his veins and these new blood cells lacked the CCR5 protein. Any HIV-1 he had in his system now had no way of making copies of itself which is why his viral load fell to the undetectable levels where they remain to this day.

Unfortunately, scientists can’t do this for everyone with AIDS. Not only is the CCR5 delta 32 mutation rare enough that it would be impossible to find donor matches for all or even most AIDS patient, but bone marrow transplants are also dangerous, expensive treatments with a high mortality rate. No, we need a different way to use this mutation to help cure other AIDS patients.

One way would be to engineer the mutation into a patient’s blood cells. Now we could avoid having to find a donor.

This is just what the folks at Sangamo Biosciences are trying to do. With the help of a team of academic collaborators and money from California Stem Cell Bond, they have come up with a product called SB-728 that can specifically inactivate the CCR5 gene in human cells. This treatment has even made it into clinical trials where so far the results appear to be encouraging (although not everyone agrees).

If this approach works, it would be a game changer for AIDS. The disease would go from being manageable to being functionally cured. And that isn’t all. There are other diseases that could be treated similarly. Success here could translate to a whole new way to get at other intractable diseases.

This is all very exciting, but I want to caution against getting our hopes up just yet. This specific treatment could still fail in ongoing clinical trials or even turn out to not be a permanent cure. But still, because of the Berlin patient, we know that if we can inactivate the CCR5 gene in a patient’s blood cells, we can cure his or her AIDS. So even if this approach fails, there may be other ways to kill this gene.

Molecular Scissor Science

Image courtesy of Dr. Stacey Wirt, Stanford University.

Image courtesy of Dr. Stacey Wirt, Stanford University.

The science behind this approach is very cool. The basic idea is to create a pair of molecular scissors that will cut human DNA only at the CCR5 gene. Once cut, our cells will wreck the gene in the process of repairing the DNA. Remember, a broken CCR5 gene means no CCR5 protein which means no HIV-1 infection.

The scissors part is easy. There are lots of enzymes whose job it is to cut DNA. The most famous are the restriction endonucleases from bacteria that serve as a part of their primitive immune system (they chop up invading viruses). In fact, molecular biology is built on these enzymes.

At the time scientists at Sangamo started working on this approach, there were no natural enzymes specific enough for their purposes. The enzymes known at this time would cut human DNA at thousands of different places which would obviously be catastrophic. The patient would not survive such treatment.
So the scientists needed to come up with a way to make these scissors only cut at the spot they wanted. There are a number of ways to do this but the scientists at Sangamo focused on natural DNA binders called zinc finger proteins.

The first step was to figure out how these zinc finger proteins recognize specific DNA sequences. With a lot of work, they came to understand this well enough that they could now create zinc fingers that recognize any three bases they were interested in. So they could whip up one that recognized ATG and another that could recognize CCC and so on.

Three base pairs isn’t enough and in fact, is worse than any of the naturally available enzymes. To get at the 18-24 base pair recognition they needed, they decided to string together multiple zinc fingers. Now they had the specificity they needed. (I have simplified this mightily but it is the basic idea…click here if you want to go deeper.)

So the scientists whipped up a protein that could specifically recognize the CCR5 gene and attached the unfortunately named Fok1 as its scissors. This protein cuts the CCR5 gene in cells in the lab and in clinical trials. So far so good.

We need to wait to see what happens, but these trials are definitely something we need to keep our eyes on. They may not only lead to a functional cure for AIDS, but they could also open up a whole new way to treat diseases.

A very nice explanation of zinc finger nucleases and a second type of scissors, TALENs.

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Category: Biology, Health

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About the Author ()

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA and runs their Stanford at The Tech program. The program is part of an ongoing collaboration between the Stanford Department of Genetics and The Tech Museum of Innovation. Together these two partners created the Genetics: Technology with a Twist exhibition. Read his previous contributions to QUEST, a project dedicated to exploring the Science of Sustainability.
  • paul nicholes

    Medical scientists have discovered a new way battle HIV/AIDS by using cuboid marrow therapy and mobile technological innovation.

  • guest1

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  • guest

    MY NAME IS MARIAM BAURICE FROM SOUTH AFRICA…I SAW THIS COMMENT ON POSITIVE BLOGS AND I WILL LOVE TO TELL EVERY BODY HOW MY STATUS CHANGES TO NEGATIVE, AND AM NOW A LIVING WITNESS OF IT AND I THINK ITS A SHAME ON ME IF I DON’T SHARE THIS LOVELY STORY WITH OTHER PEOPLE INFeCTED WITH THIS DEADLY VIRUS…,HIV HAS BEEN ONGOING IN MY FAMILY… I LOST BOTH PARENTS TO HIV,. AND IT IS SO MUCH PAIN IVE NOT BEEN ABLE TO GET OVER.. AS WE ALL KNOW MEDICALLY THERE IS NO SOLUTION TO IT..AND MEDICATION IS VERY EXPENSIVE..SO SOMEONE INTRODUCED ME TO A NATIVE MEDICAL PRACTITIONER IN AFRICA..I HAD A JOB THERE TO EXECUTE SO I TOOK TIME TO CHECK OUT ON HIM.I SHOWED HIM ALL MY TESTS AND RESULTS.. I WAS ALREADY DIAGNOSED WITH HIV AND IT WAS ALREADY TAKING ITS TOWL ON ME.. I HAD SPENT THOUSANDS OF DOLLARS SO I DECIDED TO TRY HIM OUT…I WAS ON HIS DOSAGE FOR 6MONTHS. ALTHOUGH I DIDNT BELIEVE IN IT, I WAS JUST TRYING IT OUT OF FRUSTRATION… AND AFTER 2 WEEKS, I WENT FOR NEW TESTS… AND YOU WONT BELIEVE THAT 5 DIFFERENT DOCTORS CONFIRMED IT THAT AM NEGATIVE..IT WAS LIKE A DREAM,,I NEVER BELIEVE AIDS HAS CURE..AM NOW NEGATIVE,,AM A LIVING WITNESS..I DONT KNOW HOW TO THANK THIS MAN… I JUST WANT TO HELP OTHERS IN ANY WAY I CAN..HAVE JOINED MANY FORUMS AND HAVE POSTED THIS TESTIMONIES AND ALOT OF PEOPLE HAS MAIL AND CALLED THIS MAN ON PHONE AND AFTER 2 WEEKS THEY ALL CONFIRMED NEGATIVE..BBC NEWS TOOK IT LIVE AND EVERY.. HOPE HE HELPS YOU OUT.. EVERYBODY SAW IT AND ITS NOW OUT IN PAPERS AND MAGAZINES THAT THERE’S NATIVE CURE FOR HIV AND ALL WITH THE HELP OF THIS MAN,,HAVE TRIED MY OWN PARTS AND ALL LEFT WITH YOU,,IF YOU LIKE TAKE IT OR NOT..GOD KNOWS HAVE TRIED MY BEST.ABOUT 97 PEOPLE HAVE BEEN CONFIRMED NEGATIVE THROUGH ME..AND THEY SEND MAILS TO THANKS ME AFTER THEY HAVE BEEN CONFIRMED NEGATIVE,,THIS MAN IS REAL..DON’T MISS THIS CHANCE,,HIV IS A DEADLY VIRUS,,GET RID OF IT NOW..
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    looking for a way out, and he those cast all kind of spell like ::
    Love Spells
    Luck, Money Spells
    Health, Well Being
    Protection, Healing
    Curses, Hex, Breakups
    NEW! Combo Spells
    High Priestess Spells
    Vampire Spells
    Authentic Voodoo Spells
    Custom, Other Spells
    Business spells
    Health/Healing spells
    Curse removal
    Job spells
    Healing from all kind of diseases
    Love binding
    Barrenness(need a child)
    Need love
    Lottery Spells
    Promotions
    Success
    Money rituals
    winning court case
    Divorce spells
    Low sperm count
    Infertility in women
    Breast enlargement/reduction
    Penis enlargement/reduction
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  • guest

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  • guest

    DR Ugbakhuan is the only Dr who could ever get my HIV-AIDS cured with
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    any solution on my disease, despite all these happening to me, i always
    spend alot to buy a HIV drugs from hospital and taking some several
    medications but no relieve, until one day i was just browsing on the
    internet when i come across a great post of !Michelle! who truly said
    that she was been diagnose with HIV and was healed that very week
    through the help of these great powerful healing spell doctor, sometime i
    really wonder why people called him Dr Ugbakhuan, i never knew it was
    all because of the great and perfect work that he has been doing that is
    causing all this. so i quickly contacted him, and he ask me some few
    questions and he said a thing i will never forget that anyone who
    contacted him is ! always getting his or her healing in just 6 hours
    after doing all he ask you, so i was amazed all the time i heard that
    from him, so i did all things only to see that at the very day which he
    said i will be healed, all the strength that has left me before rush
    back and i becomes very strong and healthy, this disease almost kills my
    life all because of me, so i will to hospital to give the final test to
    the disease and the doctor said i am HIV negative, i am very amazed and
    happy about the healing DR Ugbakhuan gave to me from the ancient part
    of Africa, you can email him now for your own healing too at:
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  • guest

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  • James Schwantes

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  • paul

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  • anonymous

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    thank you sir for healing me from HIV, i am Doris Carter.

  • anonymous

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  • anonymous

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  • Silva Morgan

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  • rita

    I Am Mrs lara, i live in Texas (USA).[READ MY STORY. ON HOW I GOT MY AIDS
    CURED].Truthfully, i was tested HIV + positive last 3years. I keep on managing the drugs i
    usually purchase from the health care agency to keep me healthy and strenghtful, i tried all i can too make this disease leave me alone, but unfortunately, it keep on eating up my life, this is what i caused myself, for allowing my fiance make sex to me unsecurely without protection, although i never knew he is HIV positive. So last few 4days i came in contact with a lively article on the internet on how this Powerful Herb Healer get her well and healed. So as a patient i knew this will took my life 1 day, and i need to live with other friends and relatives too. So i copied out the Dr kpelede the traditional healer’s email id: kpeledesolutiontemple@gmail.com, and i mailed him immediately, in a little while he mail me back that i was welcome to his temple home wereby all what i seek for are granted. I was please at that time. And i continue with him, he took some few details from me and told me that he shall get back to me as soon as he is through with my work. I was very happy as heard that from him. So Yesterday, as i was just coming from my friends house, Dr kpeledde called me to go for checkup in the hospital and see his marvelous work that it is now HIV negative, i was very glad to hear that from him, so i quickly rush down to the nearest hospital to found out, only to hear from my hospital doctor called Browning Lewis that i am now HIV NEGATIVE. I jump up at him with the test note, he ask me how does it happen and i recide to him all i went through with Dr kpelede. I am now glad, so i am a gentle type of person that need to share this testimonies to everyone who seek
    for healings, because once you get calm and quiet, so the disease get to finish your life
    off. So i will advice you contact him today for your healing at the above details:
    Email ID: kpeledesolutiontemple@gmail.com

  • willim

    I was been suffering hardship from HIV/AIDS since 9yrs now, and i happen to have 2 kids for my husband, and now we cannot proceed to have another kids all because of my disease and now i have do all what a human like i and my husband can do just to get my disease healed, i have went to several places to seek for help not even one person could ever help, until i melt a comment on the daily news paper that was commented by Miss Marilyn about how this powerful traditional doctor help her get cured of the disease (HIV-AIDS) ” my fellow beloved” i firstly taught having a help from a spiritual traditional healer was a wrong idea, but i think of these, will i continue to stress on these disease all day when i have someone to help me save my life?” so i gather all my faiths and put in all interest to contact him through his Email address at dr.camalahivadscure@yahoo.com , so after i have mailed him of helping get my disease cured, i respond to me fast as possible that i should not be afraid, that he is a truthful and powerful doctor which i firstly claimed him to be. So after all set has been done, he promise me that i will be healed but on a condition that i provide him some items and obeyed all his oracle said. I did all by accepting his oracolous fact and only to see that the following week Dr Camala mail me on my mail box that my work is successfully done with his powers, i was first shocked and later arise to be the happiest woman on earth after i have concluded my final test on the hospital by my doctor that i am now HIV- Negative. My papers for check are with me and now i am happy and glad for his miraculous help and power.

    With these i must to everyone who might seek for any help, either for HIV cure or much more to contact him now at these following email now,

    Email:dr.camalahivadscure@yahoo.com or visit him at http://diseasecure.webs.com

    ” sir thank you so much for your immediate cure of my disease, i must say for curing my disease, i owe you in return. Thanks and be blessed sir.

    His Email address is:

    dr.camalahivadscure@yahoo.com

  • belinda

    my name is Belinda, i want to give almighty praise to Dr OJE who help me to cure my HIV/AID, please help me to give thanks to him he is a great man who God send from heaven to save people’s life, this man also save the life of my friend who have HIV/AID, please thank this man for me, also if you have any type of problem you can also contact him to help you out on it, he is a wonderful man, his email is temple.of.solution.center@gmail.com contact him now for him to help you too, you can also reach him on phone if you are in his country Nigeria: +2348070945420