SOFTWARE UPDATE: Gene Editing Could Rescue AIDS Patients

SOFTWARE UPDATE: Gene Editing Could Rescue AIDS Patients

HIV Gains Foothold: The human immunodeficiency virus, HIV, gains entry into immune T cells by initially binding to the cell surface receptor protein CD4 and then recruiting a co-receptor, usually CCR5. Infected T cells eventually die and the patient becomes susceptible to other infections, described as acquired immunodeficiency syndrome or AIDS. 

As Luck Would Have It: About ~700 years ago, a chance mutation in the CCR5 gene appeared that inactivated the receptor. This mutation, CCR5-Δ32, has a slight negative fitness effect because CCR5 is one of many chemokine receptors important in the inflammatory immune response. The mutation should have dwindled or disappeared. Instead, the mutation underwent intense positive selection, now prevalent in ~10% of the European population. Modeling studies suggest that the mutation helped fight off small pox virus, conferring an unexpected survival benefit. Today, it provides resistance to HIV: one copy of the mutation delays AIDS onset ~ 2 years, while 2 copies confers resistance to the common HIV-1 R5 strain. 

The Berlin Patient: A famous case of “natural gene therapy” involved Timothy Ray Brown who was being treated for HIV infection in the mid-nineties. Brown then developed leukemia in 2006 and his condition deteriorated. He received a stem cell transplant from a German donor whose CCR5 genes carried the resistant mutation. Not only did the treatment cure Brown’s leukemia, it also eliminated the HIV infection (  

Gene Editing: Recent efforts are designed to be more accessible for AIDS patients. The idea is to remove T cells from the patient, manipulate the CCR5 gene to insert mutation, then re-introduce the modified T cells back into the patient. A small-size feasibility and safety study was reported this week ( involving 12 patients: 6 received modified T cells and were taken off anti-retroviral therapy for 4 weeks. The results were promising! T cell counts increased in the treatment group, and the modified cells outlasted the unmodified cells by 7-fold. The paper is behind a paywall, so please ask if you have questions!  The news story is here:

Image shows an immune T cell (yellow) in the lower right, budding off particles of HIV (green) seen in a colored transmission electron micrograph from To the upper left, is a molecule of CCR5 (yellow) embedded in the cell membrane (grey lipid) from Wikimedia (

#ScienceEveryday   #ScienceSunday  

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59 Responses to SOFTWARE UPDATE: Gene Editing Could Rescue AIDS Patients

  1. Azlin Bloor says:

    That’s great news but at the risk of being a wet blanket, we’ve been hearing the “around the corner” theories for so many things, for so long, no? Don’t hit me, Professor!

  2. Rajini Rao says:

    Azlin Bloor , fault the sensationalist press for the around the corner stories! Understandably, they do it as click bait. The reality is that science is hard, and the diseases we seek to battle have complexities beyond our understanding. That said, T cell therapy is slowly becoming a reality as treatment for cancer and immune disorders. My former student is at Memorial Sloan Kettering Cancer Inst. working with patients using their T cells to fight against leukemia.  

  3. Azlin Bloor says:

    That’s really heartening news, Rajini Rao! 

  4. That is amazing!  I shared your story with my AP students as we have just finished learning about viruses and the immune system.  I am hopeful that my students can understand the implications of this study.    I can’t help but wonder if people without science backgrounds enjoy Rajini Rao ‘s articles as much as I do!

  5. Adam Black says:

    Rajini Rao  Its been kind of obvious ( for about four years ) that gene editing the CCR5 delta-32 deletion, in combination with other techniques ( like  Vectored Immuno-  Prophylaxis * )  will yield a practical-AIDS cure.

    I also don’t understand why its taken so long to do these preliminary studies, when we finally have a potential path to a cure .

    Questions  ( Sure , I have some )

    1 what is new,  here?:

    2 Was this done on a stem-cell level ( to confer  permanent immune tcell lines ) ?

    b If no, why not?

    3 Were a significant amount of the patients cells converted?

    B) or were their old susceptible cells killed off, first ?

    4 What Techniques were used for the edit?

    ( zinc-finger nuclease or something else? )

    5 What about the CXCR4. receptor?

    a) why wont this technique put selective pressure on HIV to use the other one instead?

    B) Is it possible to block CXCR4.?

    C) Can Both receptors be safely blocked?

    6 Also about 5 years ago,  I remember an enzyme was developed that could cut supposedly HIV out of the genome of infected cells, I see that  as part of the Practical Cure Map, do you know what happened with it?

    <  * VIP is a technique which gene-edits muscle cells to produce Broadly Neutralizing antiHIV antibodies

    It hacks them into being effective immune factories, that HIV cant infect  >

  6. Jonah Miller says:

    Wow, that’s amazing!

  7. Rajini Rao says:

    Adam Black everything takes longer than expected when it involves human patients. These trials also cost money, so perhaps petition the NIH to restore funding to be better than 10% success rate?

    1) What’s new is that zinc finger nucleases were used. CRISPR will  probably be following closely. 

    2) They used autologous CD4+ T cells. This is less expensive than stem cell therapy.

    3) Up to 20% of the cells were successfully modified. They mention in the paper that their goal is to increase the efficiency of the modification. The modified cells were selected for survival in the patient because they increased in number while the unmodified T cell decreased. At the end of 4 weeks there was a 7x difference in population.

    **There was an interesting side note: One patient did exceptionally well and his viral load became undetectable, and half his T cells were replaced by the modified ones after 4 weeks. He turned out to have one copy of the mutant CCR5 already! So they are now recruiting people with one mutant copy who are likely to show the most benefit from this treatment.  

    4) Yup, commercially available ZFN is what makes this “gene editing”. 

    5) The CCR5 mutation does not provide resistance to the X4 strain that targets the other co-receptor, CXCR4. However, the latter usually associates with a later stage of HIV infection. The CCR5 variant is a natural mutation, likely selected by evolution to be effective against viral infection and also non-deleterious to the human carriers. In a way, evolution has already provided the answer to your question since carriers of the CCR5-delta32 mutations are resistant to HIV. This means that physiologically, CCR5 is important for HIV-1 infection. 

    C) I don’t know if there are studies looking at knockout of both receptors (I’m guessing there are). But there are many ways to bell this cat. Drugs are being developed to target these receptors. Other polymorphisms in the genes for the natural ligands, like RENTES, are associated with HIV resistance or susceptibility. In other words, high levels of the natural binding partner of these receptors can compete out the virus, and not enough makes it easier for the virus to get into the T cells.   

    6) I don’t know about this VIP technique but I did a search on PubMed for David Baltimore and came up with this 2014 paper that just came out:

    Let me know if you want a copy of it, since it is behind a paywall.

    Edit: This free read is a great review of the challenges in replicating stem cell therapy used on the Berlin patient

  8. Rajini Rao says:

    Shannan Muskopf , let me know if your students found any part of this confusing. I’m not a virologist by any stretch, but I can attempt to answer them 🙂

  9. Rajini Rao says:

    Let’s hope so, L McGarity . My former student was describing the aseptic procedure for T cell apheresis: unbelievably tedious but critical to avoid inadvertently contaminating the sample. 

  10. Jim Carver says:

    L McGarity And once they get the Good Housekeeping Seal of Approval it will be on the store shelves in days.

    (Sorry, I couldn’t resist.) 

  11. Rajini Rao says:

    L McGarity that sounds interesting, would love to hear more about your experience.

  12. Tom Lee says:

    Good news. Amazing result . 🙂

  13. Rajini Rao says:

    Thanks, good to see you Tom Lee 🙂

  14. Rajini Rao says:

    Oh, do tell, L McGarity 😉

    Paul Wakfer , this is an expensive and risky procedure. I’m guessing it would be used on cases where retroviral therapy is not good enough or who may be particularly good candidates?  

  15. woooww..good news Rajini..thank you for sharing it..:)

  16. Rajini Rao says:

    I enjoyed reading up about the topic, Karin Frauenfeld . Progress seems to be slow but sure! 

  17. Superb information Rajini Rao. Thank you so much.

  18. Rajini Rao says:

    You’re welcome, R Prakash Prakash . Hope you are doing well 🙂

  19. Shannan Muskopf I, for one, thoroughly enjoy Rajini Rao’s posts and seriously try to learn. And she is very kind to accommodate my ignorant questions too.

  20. E.E. Giorgi says:

    that is indeed awesome news, the problem is that this kind of therapy is too expansive for the 25 million people in Africa who are affected by HIV/AIDS 😦

  21. Rajini Rao says:

    E.E. Giorgi , very true. Unfortunately, the resistance allele is conspicuously absent from the African continent. 

  22. Rajini Rao says:

    Let me search for it, L McGarity .

  23. Rajini Rao says:

    I know the feeling! I also found this, but it is on killer T cells not antibodies:

  24. Rajini Rao says:

    Just some Google-fu 😉

    The study of HIV is so complex and interesting. We have a big group working on HIV in my university. I’m usually blown away by their projects. 

  25. Shannan Muskopf There are some that enjoy the articles. I am one. My science background is very limited. However, it is expanding. Rajini Rao is very professional and informative in her posts. Add the extra benefit of her interaction also great comments from the readers and I leave with a better understanding. Afterall, knowledge is the stepping stone to understanding, and understanding the path to wisdom. I thank all of you .:-)       

  26. Rajini Rao says:

    Garron Longfield , thanks. You bring up a wonderful point on comments from readers. These typically send me searching the literature for answers and discovering new ways of looking at a problem. I wouldn’t be here if I didn’t love (and learn) from this too 🙂

  27. Rajini Rao says:

    Drew Sowersby especially for cancer, where there is no parallel to the success of HIV antiretroviral drugs. I’m hopeful that biomolecules and genetic engineering will help.  

  28. Rajini Rao, the posts and comments also send me on a foray of research. Your sharing of information  many times gives me a starting point. However, I tend to get side tracked and spend hours doing this. I once had a fellow student describe me as; a person who seems to have an unquenchable thirst for knowledge.This did help in college,but not much socially. lol.


  29. Rajini Rao says:

    Garron Longfield hah, the perfect “type” for G+. We’ve all been down that rabbit hole 🙂 

  30. thanks for information and share..

  31. Adit Morey says:

    The gene-editing therapy looks very promising in treatment if HIV, though it is still in it’s nascent stage.

    I find the process of gene-editing very analogous to permutations and combinations – the changed arrangement of genetic code to assist in curing untreatable medical conditions using one element (here, CCR5) of the gene itself although the element is selected after lot of research and hard work.

  32. Mary T says:

    Totally awesome post!

  33. Mike Gleason says:

    I wonder at what point during hematopoiesis the T cell gains the receptor, or if it’s always there. Would it make any difference if the gene modification was done to a progenitor lymphoblast?

  34. Henk Poley says:

    The bone marrow transplant apparently isn’t 100% effective:

    Though the article is not very clear if the HIV recurrence is due to viral adaptation around the CCR5 receptor mutation.

  35. Rajini Rao says:

    Henk Poley the article is confusing. They don’t say whether the bone marrow transplant was from a donor with the CCR5-delta32 mutation at all. The article does make a good point about risk vs. benefit of bone marrow transplants, although even Faucci’s statement sounds muddled to me (!). I believe he is saying that if you have a tumor and HIV infection, then it is worth getting a bone marrow transplant, but if you just want to get off antiretroviral drugs, then its not worth the risk. The advance with this gene editing technique is that it is not as expensive or risky and a bone marrow transplant.  

  36. Rajini Rao says:

    Mike Gleason good point- if the CCR5 editing was done in a pluripotent cell, then it should have the advantage of being regenerated, instead of having a defined life time like these cells. 

  37. Tiffany Ha says:

    reminds me of grapes, potato chips, and egg noodles 🙂

  38. Great news!! Thanks Rajini Rao  for the updates 🙂

  39. E.E. Giorgi says:

    Rajini Rao did you hear? Dr. Persaud’s group treated another HIV-positive newborn just like the little girl that made news last year,  and even though the infant is still under therapy (she’s only 9 months old), her viral loads are still undetectable

    news story here:

  40. Rajini Rao says:

    E.E. Giorgi this is excellent news. Good to hear that they could duplicate the first success (I’m sure many groups are trying this now). Deborah Persaud is right here on my home ground but I’ve not met her 🙂

  41. Adam Black says:

    E.E. Giorgi So far that story is more Click-bait Journalism and Science PR , than rigorous science.

    “and even though the infant is still under therapy (she’s only 9 months old), her viral loads are still undetectable”  Which is true for millions of people around the world.

    just like the little girl that made news last year

    Actually the 2 cases are very different. So far this news is very premature.

    What is news,  is the newborn didnt seroconvert.

    The mother in the first case had a full immune system with  a very high amount of Tcells ( for being un-medicated ) . In this case, the mother had  a much later-stage disease.

  42. Rajini Rao says:

    Adam Black , I would not classify that article as click bait and certainly, I would not call out E.E. Giorgi for linking to it. The article explains clearly, “Doctors gave the baby high doses of antiretroviral drugs — AZT, 3TC and Nevirapine — four hours after birth. Eleven days later, the virus was undetectable in her body and remained undetectable nine months later.

    The California baby is still on antiretroviral treatment, so it’s too soon to tell if the child is actually in remission.”Taking kids off antiretroviral therapy intentionally is not standard of care,” said Dr. Deborah Persaud, a virologist with Johns Hopkins Children’s Center who has been involved in both cases. “At this time, there is no plan to stop treatment.”

    She goes on to explain that a clinical trial to test the effectiveness of this early treatment technique on infants born with HIV is starting soon. 

    This reads like a well balanced report to me. What part of it sounded like hype to you? 

    The initial publication on the early treatment technique was based on a sound premise, as I recall. 

  43. Adam Black says:

    Rajini Rao  I did not mean the article itself  was necessarily clickbait, nor as criticism of E.E. Giorgi .  My intent was to use the terminology you used previously about irresponsible HIVscience  stories .

    I was implying that the story behind it  was based on on a press release designed to generate headlines, by conflating it with the previous one. Which it has succeeded in doing. I was deceived by reading shorter stories of the same event

    I had just finished reading a critical article of it, when I wrote that; but I forgot where, ( NYT? Daily beast? )  so I didnt provide the link.

    I do agree with the article ( which at the moment I am not linking to ) that finds fault with irresponsible science press releases. I have noted that genuine cure research almost never calls itself that ( which your story falls under) ; While examples of  highly theoretical research , with zero justificaton it might even lead to a successful treatment at all, brazenly uses the Cure-word to the press.

  44. E.E. Giorgi says:

    Adam Black , I happen to work in the HIV field, and I followed the story of the first baby very closely. I’m in Los Alamos, I work on the HIV database. Even though this new case is not quite the same as the previous one, we are very excited about it. I agree with Rajini Rao , I found the report very balanced. Neither baby has been “cured” in the literal sense of the word, still,  any step forward, no matter how small, deserves celebration in this field. Plus it teaches a lot about HIV in general. Could it possibly be that if we are able to catch the virus within hours of infection, we can actually stop the infection using drugs? I don’t know the answer, but I think it’s a good thing that we keep asking the question.

  45. E.E. Giorgi says:

    Also, I don’t know if it’s true about “millions of people” as you claim. It is true that some people are able to get their viral loads down to undetectable when started on teh cocktail of anti-retroviral drugs, however, all of those people’s viral loads bounce back almost immediately when they go off the drugs , and the virus gets more virulent because it has developed drug resistance. The baby from last year’s news made the news because she’s drug-free and her viral loads are still undetectable. It’s too early to tell for this new baby, but it’s very exciting that doctors are trying to reproduce the case. 

  46. Good to see we are moving forward in helping AIDs patients – apart from that I also love these kinds of scientific drawings. 🙂

  47. Rajini Rao says:

    Bente Lilja Bye , coincidentally the golden colors of the helical protein matched the cell image perfectly, and I was inspired to put them together and write the post 🙂

  48. Adam Black says:

    Update : The baby is not cured…

  49. Adam Black says:

    Rajini Rao I have an important question related to this. 

    I have been critical of the develpoment of the class of HIV antivirals known as Entry-inhibitors which use this knowledge to block the CCR5 receptor. ( Maravoc ) 

     My criticism is that this will inevitably ( like all HIV drugs ) lead to mutations and drug resistance this wasting a viable practical cure path on a temporary HIV drug.

    My Question is:  Am I wrong? 

    Will users of Miravoc still be able to avail themselves of this ( delta 32 gene therapy ) ,  as a practical solution/cure?

    Does Miravoc lead to mutated HIV that can bypass this receptor ( x4)  ?

  50. Rajini Rao says:

    Adam Black this post is not about the Mississippi baby with HIV. There was no T cell therapy done in her case. 

    I’ll take a look at your question later, I’m traveling out of the country with limited internet access. 

  51. Adam Black says:

    Rajini Rao oh, ok.  ( Oh I know that. ) 

    Thanks you Rajini Rao 

  52. Adam Black says:

    Zombie Post. But…

    Rajini Rao​ I read a lot of HIV research but I still dont have an answer to that question.

    The effects of Mirovic resistance and mutations against Entry Inhibitors

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