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CRISPR gene-editing eliminates HIV in mice

08 May 2017

By Emma Laycock

Appeared in BioNews 899

US scientists have used CRISPR gene-editing to remove HIV DNA from the genomes of living animals, eliminating further infection.

For the first time, CRISPR/Cas9 has been shown to shut down replication of HIV and to eliminate the virus from three animal models, one a 'humanised' mouse. The research, which was published in Molecular Therapy, builds on earlier work where the researchers used CRISPR to cut HIV DNA out of the genomes of transgenic rats and mice.

'Our new study is more comprehensive,' said co-lead researcher Dr Wenhui Hu at Temple University, USA. 'We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells.'

HIV permanently inserts its own genome into the DNA of infected cells. Anti-retroviral therapy aims to reduce the amount of virus produced by an infected person, but cannot eliminate the virus. Copies of HIV can persist in long-lived T-cells and other tissues, providing hidden reservoirs for infection.

Researchers used a modified virus to deliver the CRISPR/Cas9 system into the cells of infected mice. Scientists simultaneously targeted four different HIV sequences, making it harder for the virus to escape elimination by mutating its DNA (See BioNews 846). After treating the mice, researchers tested the levels of HIV RNA. A new imaging system was also used to observe viral replication in real-time and to see latent HIV reservoirs.

The team tested their gene-editing strategy in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1 (the most common subtype of HIV), and found a 96 percent excision efficiency.

'With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection,' Dr Kamel Khalili, co-lead researcher at Temple University explained. This provides the first evidence for eradicating HIV-1 prophylactically with a CRISPR/Cas9 system.

Latent HIV-1 infection was mimicked in humanised mice. 'These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection,' Dr Hu explained. After a single treatment, the latently infected human cells no longer contained HIV DNA.

Dr Paul Volberding, director of the amFAR Institute for HIV Cure Research, not involved in the study, told CBS: 'The basic science community in HIV research is now very focused on finding a cure. It still feels a long way off but the tools we now have, definitely including the gene editing used in this report, is accelerating our work and raising optimism.'

'The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease,' Dr Khalili said. 'Our eventual goal is a clinical trial in human patients.'

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