U.S. researchers said Monday they have successfully removed HIV DNA from the genomes of living animals using a gene-editing tool, giving scientists a boost in confidence to eventually eliminate the AIDS virus infection in human patients.
In a new study published in the journal Molecular Therapy, researchers at Temple University and the University of Pittsburgh reported performing the feat in three different animal models, including a "humanized" model in which mice were transplanted with human immune cells and infected with the virus.
The team is the first to demonstrate that HIV-1 replication can be completely shut down and the virus eliminated from infected cells in animals with a powerful gene editing technology known as CRISPR/Cas9.
The new work followed a previous proof-of-concept study that the team published in 2016, in which they used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals' bodies.
"Our new study is more comprehensive," Wenhui Hu, associate professor at Temple University, who led the study, said in a statement.
"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."
In the new study, the team genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60 to 95 percent, confirming their earlier findings.
They then tested their system in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1, and found the excision efficiency of their strategy reached 96 percent in these animals.
In the third animal model, latent HIV-1 infection was recapitulated in humanized mice engrafted with human immune cells, including T cells, followed by HIV-1 infection.
"These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection," Hu explained.
Following a single treatment with CRISPR/Cas9, viral fragments were successfully excised from latently infected human cells embedded in mouse tissues and organs, he said.
Next, the team planned to repeat the study in primates, a more suitable animal model where HIV infection induces disease, with an eventual goal of conducting a clinical trial in human patients in the future.
