Using gene editing technology, researchers at the Lewis Katz School of Medicine at Temple University have, for the first time, successfully excised a segment of HIV-1 DNA -- the virus responsible for AIDS -- from the genomes of living animals. The breakthrough, described online this month in the journal Gene Therapy, is a critical step in the development of a potentially curative strategy for HIV infection.
"In a proof-of-concept study, we show that our gene editing technology can be effectively delivered to many organs of two small animal models and excise large fragments of viral DNA from the host cell genome," explained lead investigator on the study, Kamel Khalili, PhD, Laura H. Carnell Professor and 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 (LKSOM).
Current treatment for HIV infection is centered on the use of a combination of antiretroviral drugs. While antiretroviral drug therapy can effectively suppress HIV replication, it has no ability to eliminate HIV-1 from infected cells. Moreover, when antiretroviral therapy is interrupted, HIV replication rebounds, placing patients at risk for developing acquired immune deficiency syndrome, or AIDS. Such latent infections develop because HIV DNA is able to persist in the genomes of CD4+ memory T-cells and perhaps in other cellular reservoirs where the virus remains silent and is unaffected by current therapy.
In earlier research, Dr. Khalili and colleagues were able to show that their novel gene editing system, which is based on CRISPR/Cas9 technology, has the extraordinary ability to eliminate HIV-1 from infected cells in vitro with no adverse effect on the host cells. In ex vivo experiments using clinical specimens, including T-cells from patients infected with HIV that were expanded in culture, they showed that viral replication was significantly reduced following treatment with the gene editing system.