Gene Editing: Moving HIV Cure Research Forward

Segment Description: Eric Daar, MD, chief of the Division of HIV Medicine, Habor-UCLA Medical Center, explains how gene editing therapy can be used to move the HIV cure agenda forward.

Interview Transcript (modified slightly for readability):

“Gene editing therapy in the realm of HIV has become an area that has gotten a lot of attention—as has gene editing in many other areas—and a lot of that is based on some new advances in the technology in the ability to simplify our goal of trying to edit certain genes.

From the HIV perspective, I would say the area of which there’s the greatest interest is as we move forward in the realm of cure research. HIV treatment has gotten so effective and easy to take, the natural next step is to try to cure people. What we’ve learned over the last several years is there are some obstacles to doing that. One of the major obstacles is that we have this persistent reservoir virus within the body. And so, once someone is infected, they have this, and people have been attempting to learn more about it.

There’s 1 known example of an individual that has been cured of HIV—the so-called ‘Berlin Patient.’ The things that were unique about what the Berlin Patient underwent was: one, he was known to be HIV infected and he was suppressed on antiretroviral therapy but based on our experience, we know [he] was not cured. He developed acute leukemia and part of his treatment required a stem cell transplant or bone marrow transplant, and he had very progressive oncology specialists in Germany where he was diagnosed. They were able to identify a donor who had this unique, inherited genetic defect, where they didn’t express an important receptor for HIV on the surface of the cells, so-called CCR5. This was an individual who acquired this deleted gene from both the mother and the father. And we know that both of these individuals who represent maybe 1% of the Caucasian population, are relatively resistant to HIV infection.

And so, the Berlin Patient underwent intensive chemotherapy and radiation therapy and the stem cell transplant. He ended up relapsing with his leukemia, went through the whole process again, was sick as a dog and stopped his antiretroviral therapy because he was so ill, but ultimately went into remission for his leukemia.

They went to restart his antiretroviral therapy and they did a viral load and there was no virus there. And so, the thought was there were probably a variety of things that this individual went through that resulted in him [to be], what we believe is cured now; it’s probably going on 9 or 10 years where he’s been off therapy with[out] any hint of virus rebounding or in his body.

And 1 of the possibilities was it was the unique bone marrow that had this mutated gene. Now, the problem is, you can be born with it if you’re lucky enough, but most people don’t have it. A bone marrow transplant is not a viable option moving forward. The obvious next step is if we think that was an important part of the cure in the Berlin patient, is to try to see if we can induce that.

Gene editing, in 1 form or another, provides an opportunity to do that in people who weren’t lucky enough to be born with this mutation. What you can do is, you can introduce something called Zinc finger endonuclease, or you can use this new technology called CRISPR that can allow you to target the CCR5 gene—and it’s normal in most people—so that it becomes abnormal, much like what the Berlin patient received in their bone marrow transplant from individuals born with 2 abnormal genes. And so, you basically take the patient’s cells out of their body, particularly the CD4 cells that target for HIV that require CCR5 and you do gene editing so that that cell population no longer expresses CCR5—and this can be successfully done in a laboratory—and then these cells can be reinfused into the body.

That, I think, is the main area of interest is right now—although there may be others—that people are really thinking about [when it comes to] gene editing and trying to see if we can move the cure agenda forward.”