|HIV particles infecting a human T cell--Courtesy of NIH/NIAID|
Finding a cure for HIV has been a priority since its emergence in the 1980s, but the virus' ability to hide itself within infected cells makes it challenging to attack. Using CRISPR/Cas9, scientists from Temple University's Lewis Katz School of Medicine have safely cut out HIV from the genome of human T cells, with eyes on a possible cure in the future.
In the past, researchers have tried to tackle latent HIV by causing it to reveal itself, thereby provoking an immune response, but so far, these "shock and kill" tactics haven't worked. The Temple team has previously used CRISPR to eliminate HIV from a human cell line, the university said in a statement. This time, they tested it on CD4 T-cells taken from patients with HIV and grown in a culture.
The study, published in Scientific Reports, showed that the technology not only eliminated the HIV from the DNA of infected cells, but also protected those cells from reinfection with no toxic effects on the cells themselves, said Kamel Khalili, senior investigator on the study. Because editing the cells' DNA is effectively mutating it, Khalili's team used ultra-deep whole-genome sequencing to check for mutations outside of their target. There were none.
|Kamel Khalili, chair of the Department of Neuroscience, director of the Center for Neurovirology, and director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University|
"These experiments had not been performed previously to this extent," Khalili said. "But the questions they address are critical, and the results allow us to move ahead with this technology." The results suggest that a cure for HIV-1 infection should "include methods that directly eliminate the proviral genome from the majority of HIV-1-positive cells, including CD4+ T-cells, and protect cells from future infection, with little or no harm to the host," the team said in the study abstract. Such a cure would eliminate the lifelong dependence of HIV patients on antiretroviral drugs.
In March 2015, Salk Institute scientists used CRISPR to chop up active and dormant HIV, removing the virus from 72% of cells and tamping down on latent HIV's ability to emerge later. Other recent approaches to tackle latent HIV include using a generic alcoholism drug to activate and flush out dormant HIV for destruction, and DART therapy, which binds HIV-infected cells to T-cells, which should then destroy the infected cells.