With the Genschere against HIV?

Combination therapy with drugs and CRISPR / Cas9 eliminates the AIDS virus in mice

HIV: To date, there is no cure for infected patients. © Nopparit / istock
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New therapeutic approach: A combination treatment of antiviral drugs and the gene scissors CRISPR / Cas9 could cure HIV infections. As a first study with mice suggests, this genetic engineering tool can be used to remove virus DNA from body cells. Thus, the gene scissors creates what is not possible with common antivirals - and seems to be able to completely eliminate the pathogen in combination with these agents.

With the help of antiviral drugs, HIV patients today can lead a largely normal life - but they must never give up the funds. The reason: common antivirals are able to significantly reduce the viral load in the body. But they do not completely eliminate the pathogen. "The HI virus integrates its own DNA into the genome of the host's immune cells. It can survive in a latent form and be reactivated at any time, "said Prasanta Dash of the University of Nebraska in Omaha and his colleagues.

Medicines plus CRISPR / Cas9

In order to cure the infection, therefore, all infected cells would have to be eliminated or the injected, proviral DNA would be removed from them. But how can that succeed? The researchers around Dash had the idea to try this with the Genscher CRISPR / Cas9 - the new universal tool of genetic engineers. They tested their approach on HIV-infected mice that had human T cells thanks to gene manipulation.

In a first step, the rodents were treated with special antiviral drugs, which can release their active ingredients timed and effectively inhibit the proliferation of the virus for a long time. This pretreatment was then followed by the use of gene clipping. She cut the foreign DNA out of the infected cells and thereby eliminated the last traces of the pathogen. According to the team, it was the first time that this tool removed HIV DNA from the cells of a living animal.

No longer detectable

But how well had this treatment worked? As the scientists report, the HI virus was no longer detectable in at least five out of 13 mice after the end of therapy. Even five weeks later, the pathogen could neither be detected in the blood, nor in the lymph tissue or in the bone marrow of the animals. And when the researchers transmitted immune cells from these rodents to non-infected conspecifics, nothing happened. display

Mice that had only been treated with medications or only with the gene scissors, on the other hand, still had HI viruses in measurable amounts in their bodies. "Our work shows that it takes both for a potential cure - CRISPR / Cas9 and virus suppression, " states co-author Camel Khalili of Temple University in Philadelphia.

"Elimination is possible"

Although it is still unclear why not all mice could be cleared of the disease - nevertheless, Dash and his colleagues consider their results promising: "We provide evidence that permanent virus elimination is feasible. This is an important first step on a long journey. "

Further research now needs to show how effective and safe the method is, and whether it may someday be used in humans as well. "We will now seek to experiment with non-human primates and clinical trials with human patients, possibly within a year, " says Khalili. (Nature Communications, 2019; doi: 10.1038 / s41467-019-10366-y)

Source: Nature Press / Temple University Health System

- Daniel Albat