CRISPR/Cas9 Eradicates HIV-1 Infection in Live Animals

A permanent cure for HIV infection remains elusive due to the virus’s ability to hide away in latent reservoirs. But now, in new research published in the journal Molecular Therapy, scientists at the Lewis Katz School of Medicine (LKSOM)  at Temple University and the University of Pittsburgh show that they can excise HIV DNA from the genomes of living animals to eliminate further infection. They are the first to perform 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 builds on a previous proof-of-concept study that the team published in 2016

“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.”

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.

“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.” The excision efficiency of their strategy reached 96 percent in EcoHIV mice, providing the first evidence for HIV-1 eradication by prophylactic treatment with a CRISPR/Cas9 system.

The work was led by Wenhui Hu, MD, PhD, currently Associate Professor in the Center for Metabolic Disease Research  at LKSOM; Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Won-Bin Young, PhD. Dr. Young was Assistant Professor in the Department of Radiology at the University of Pittsburgh School of Medicine at the time of the research. Dr. Young recently joined LKSOM.

Source: https://medicine.temple.edu/