Scientists have cured living animals of HIV using CRISPR gene-editing, a new study claims.
The virus remains elusive due to the its ability to hide away in latent reservoirs. But now, in new research published this week, US scientists showed they could completely remove HIV DNA from human cells implanted into mice — preventing further infection.
It is the first time scientists have ever achieved complete elimination in animal models — paving the way to a human clinical trial.
Most exciting, the study by at the Lewis Katz School of Medicine at Temple University and the University of Pittsburgh involved a ‘humanized’ model in which mice were transplanted with human immune cells and infected with the virus.
The new work, led by Dr Wenhui Hu at LKSOM, builds on the same team’s previous research, in which they managed to delete HIV-1 from the genome of most tissues. A year later, they have been able to eliminate the virus from every tissue.
‘Our new study is more comprehensive,’ Dr. Hu said.
‘We confirmed the data from our previous work and have improved the efficiency of our gene editing strategy. 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.’ The team tested three groups of mice.
- In the first, they infected mice with HIV-1.
- In the second, they infected mice with a severe case of EcoHIV (the mouse equivalent of human HIV-1).
- The third used a ‘humanized’ mouse model, engrafted with human immune cells, that was infected with HIV-1.
Treating the first group, they managed to genetically inactivate HIV-1, reducing the RNA expression of viral genes by up to 95 percent, confirming their earlier findings.
The second group has an added challenge: the virus is more prone to vociferously spread and multiply.
‘During acute infection, HIV actively replicates,’ Dr Khalili explained. ‘With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection.’ Their strategy eliminated 96 percent of EcoHIV from the mice, providing the first evidence for HIV-1 eradication with a CRISPR/Cas9 system.
Finally, they came to the third animal model: humanized mice engrafted with human immune cells, including T cells, which is where HIV tends to hide.
‘These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection,’ Dr. Hu explained.
Following a single treatment with CRISPR/Cas9, the scientists managed to completely remove viral fragments from the latently infected human cells embedded in mouse tissues and organs. The new study marks another major step forward in the pursuit of a permanent cure for HIV infection.
‘The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells,’ Dr. Khalili said.
‘Our eventual goal is a clinical trial in human patients.’