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March 2024

Media coverage:

Scientists say they can cut HIV out of cells – Michelle Roberts, BBC, March 20, 2024

HIV cure breakthrough as virus eliminated from cells in laboratory – Nina Massey, The Independent, March 20, 2024

Hopes of HIV cure after breakthrough using gene-editing ‘scissors’Sky News, March 20, 2024

Original source:

HIV in cell culture can be completely eliminated using CRISPR-Cas gene editing technology, increasing hopes of cure – European Society of Clinical Microbiology and Infectious Diseases, Press Release, March 19, 2024

TAG’s commentary:

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) decided to issue a press release yesterday about a laboratory HIV study using the CRISPR gene editing tool, more than a month ahead of the conference in Spain at which the results will be presented. A bolded, underlined note on the release suggests that the motivation was cynical advance promotion of the event: “Please credit the congress if you use this story.”

The press release has inevitably prompted a slew of media stories, none of which could obtain independent expert comments on the results because the results haven’t been presented yet. For the same reason, community-based HIV organizations are unable to give informed answers to questions about the media coverage.

People living with HIV, who have the largest stake in cure research, are left with clickbait headlines and speculation. This situation happens too often and is unacceptable — all the more so in this case, given that the conference presentation won’t occur until the end of April.

The study employed the CRISPR/Cas system, a bacteria-derived tool that has generated excitement and attention because of a potential to edit genetic code with relative precision. Therapeutic promise has already been reported in some settings, with a treatment for sickle cell disease and beta thalassemia (which modifies cellular genes outside of the body) recently approved by the U.S. Food and Drug Administration.

A leading idea in HIV cure research is to use CRISPR/Cas to try to excise or disable the virus’s genetic code in the infected cells that make up the HIV reservoir in people on antiretroviral therapy (ART).

The research group of Kamel Khalili at Temple University has published extensively on this topic, leading to a candidate approach entering a small phase I clinical trial in people with HIV (see prior media monitor entry) and the formation of a Martin Delaney Collaboratory, CRISPR for Cure.

The ESCMID press release is about the work of researchers at the University of Amsterdam who are also investigating the anti-HIV potential of CRISPR/Cas.

Dr. Elene Herrera-Carrillo and colleagues have previously reported that use of a variant called CRISPR/Cas12a led to “extinction of all infectious HIV in cell culture” and it’s not clear whether the new press release’s headline-generating claim that “HIV in cell culture can be completely eliminated” is describing a meaningfully different outcome. In other words, it appears unlikely that the new laboratory results represent a “breakthrough” as some headlines claim.

The press release notes that Dr. Elene Herrera-Carrillo’s group is working to better target CRISPR/Cas to the cells that contain HIV, and some information on this approach has already been published. The strategy is to create adeno-associated virus (AAV) vectors that enter cells expressing CD4 and CD32a, molecules which may preferentially identify cells containing HIV (previous studies of CD32a as a marker of the HIV reservoir have produced seemingly conflicting findings).

Hopefully the laboratory results will turn out to be encouraging when presented. There does appear to be consistency with the historical reports from Kamel Khalili’s group describing CRISPR/Cas anti-HIV activity in laboratory culture, but Dr. Elene Herrera-Carrillo and colleagues haven’t yet advanced their approach into animal model studies. There remain concerns about the safety and precision of CRISPR gene editing in HIV. Results from the ongoing phase I trial in the U.S. — expected later this year — should shed considerable light on the potential to translate the laboratory science into viable therapeutic candidates.

 

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