Recent estimates by the United Nations say as many as 36.7 million people worldwide are known to have HIV. Of these, roughly 1.2 million people are in the United States, according to the Centers for Disease Control and Prevention (CDC). These alarming numbers actually grow every year, and adequate treatment — let alone a cure — still seems a long way off. One of the major reasons that’s so is because HIV as a disease is something of a tough nut to crack: the virus is capable of hiding itself in latent reservoirs, making it extremely difficult for a permanent cure to be developed.
There’s a glimmer of hope, though: scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh published a study in the journal Molecular Therapy showing it’s possible to surgically remove HIV DNA from a living animal genome. This is the first time that such a method was demonstrated to be possible, and it could increase the chances of eliminating HIV infection.
The secret is in CRISPR/Cas9, the world’s most efficient and effective gene editing tool, which made it possible to delete targeted HIV-1 fragments from the infected animal tissue genome. “CRISPR-associated protein 9 (Cas9)-mediated genome editing provides a promising cure for HIV-1/AIDS,” the study’s abstract notes. This research built on a proof-of-concept study that the same team of researchers conducted last year.
“Our new study is more comprehensive,” LKSOM’s Wenhui Hu explained. “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 researchers used CRISPR/Cas9 to shut down HIV on three sets of animal models: one performed on transgenic mice with HIV-1, another with mice acutely infected with the mouse equivalent of human HIV (ecoHIV), and a third group of mice that had human immune cells with latent HIV-1 embedded into their tissues and organs.
In all three animal models, the researchers were able to successfully render HIV inactive via gene editing, reducing the RNA expression of viral genes by up to 95 percent in the first model, and up to 96 percent in the second. For the third model, they were able to remove viral fragments from the latently infected human cells in the mouse organs after only a single CRISPR/Cas9 treatment.
Now, researchers need to make the treatment more viable for humans: “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,” said researcher Kamel Khalili. “Our eventual goal is a clinical trial in human patients.”
As this is the first time gene editing was demonstrated to work on HIV in animals, this method could prove to be a game changer in treating the elusive virus: it’s a crucial step in, eventually, creating a cure.