Ben Berkhout, PhD: CRISPR-Cas Based Therapy for HIV


Ben Berkhout, PhD, discusses if CRISPR/Cas9 will be a new antiviral strategy for the eradication of HIV.

At the European Clinical Congress of Microbiology and Infectious Disease (ECCMID 2019), Contagion® spoke with Ben Berkhout, PhD, head of the laboratory in the Department of Medical Microbiology at AMC, University of Amsterdam, the Netherlands, about his symposium presentation on CRISPR-Cas9 as a new antiviral strategy for the eradication of HIV.

Interview transcript (modified slightly for readability):

Contagion®: What is the most important message that you tried to convey in your presentation?

Berkhout: Yeah there are I guess 2 messages, 1 of them is that indeed we are were able, after optimization of this CRISPR-Cas technology, to sterilize cell cultures in the laboratory from infectious HIV-1. By doing so, we actually discovered a novel mechanism, how the virus is inactivated, so that's nice for a scientist. But, of course, the main question is can we develop this a therapy. I can show great success in the laboratory, but talking about treating a patient's the first question, is where do we want to deliver this therapy? Where is this virus hiding? Actually, despite many years of research, we don't really know where this so-called HIV vulnerable reservoir is and there was a very prominent paper published 2 years ago in Nature by a group from France (Montpellier) and they published a new potential marker of this reservoir.

The interesting thing is there are many top laboratories in the last year have jumped on this and they could not reproduce the finding. So, by now, most people in the field don't believe in this marker anymore. But, in the meantime, we also started working on this on this new molecule and actually, we have become a firm believer of this molecule and again that's nice for science but it's also very nice because you want to use this molecule to target the reservoir where the virus is hiding. So, on the one hand, we have big success with CRISPR-Cas in the laboratory and we slowly are moving now towards the in vivo applications which is still very difficult.

Contagion®: What are some areas that need to be researched further in this field?

Berkhout: Of course, there's always the question of safety, so despite the success that we had in cell culture this was vicious we're a CRISPR-Cas system is delivered for good and it's active for forever. That's probably why it is so effective, but of course, concerning safety, I would not easily propose to do the same thing in patients. Because if CRISPR-Cas is hanging around in the body of a patient and it will leave some DNA, now and then, you can expect there will be potential off-target effects, toxic effects in the long run.

So, we actually have to move to totally different CRISPR-Cas technologies that only will deliver CRISPR-Cas for [trenchant] action. It has to inactivate HIV-1 and then it should be inactive for the rest of the patient's life, so that's what 1thing we are working on.

And, of course, targeting of this reservoir, in this case, the CD32 cells, we think these are the cells to target but how together that that's another important thing that we plan to work on. We will employ 1 of these well-known factor systems that people use in gene therapy factors, but we have to change them such that they will specifically go for these CD32+ cells so these are 2 of the things that have to be done better there's probably much more.

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