PHILADELPHIA—Researchers at Temple University have confirmed that their latest research on HIV has managed to remove DNA of the HIV virus from living tissue for the first time in a breakthrough that could lead to an outright cure.
In 2014 editions of the Florida Agenda, we reported that school researchers, lead by Temple University professor Kamel Khalili, PhD, were working on removing the HIV virus from the cells of rats. At that time, it was discovered that their novel gene editing system had the extraordinary ability to eliminate HIV-1 from infected cells with no adverse effect on the host cells. Those test tube in vivo experiments using clinical specimens, including T-cells from patients infected with HIV that were expanded in culture, showed that viral replication was significantly reduced following treatment with the gene editing system.
Last April, in the medical journal Gene Therapy, the team reported that they had successfully completely removed HIV from several organs of infected rats and mice.
Now the Florida Agenda has learned that the same researchers have used gene-editing technology to remove the virus from live animals.
According to Khalili, the director of the college’s Center for Neurovirology Department, “In a proof-of-concept study, we show[ed] 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.”
Current treatment for HIV infection is centered on the use of a cocktail of antiretroviral drugs. And while these drugs have allowed HIV to be a manageable disease, the drugs are only capable of suppressing the virus’ ability to replicate, and do not destroy it completely.
Unfortunately, when antiretroviral therapy is interrupted, HIV replication rebounds, placing patients at risk for developing acquired immune deficiency syndrome, or full-blown 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 the latest studies, the edited gene of the HIV DNA was introduced into living rats and mice, and within two weeks had managed to completely eliminate the virus in every tissue, including the brain, heart, kidney, liver, lungs, spleen, and blood cells.
“The ability of the delivery system to enter many organs containing the HIV-1 genome and edit the viral DNA is an important indication that this strategy can also overcome viral reactivation from latently infected cells and potentially serve as a curative approach for patients with HIV,” said Dr. Khalili. The study, which was performed on the most common form of the HIV-1 virus eliminates any chance for the development of replication-competent virus or escape events.
The clinical implications of the new study are far-reaching. The gene editing platform is likely not only capable of eradicated HIV-1 DNA from patients, but it is also highly flexible and potentially could be used in combination with existing antiretroviral drugs to further suppress viral RNA. It also could be adapted to target mutated strains of HIV-1.
Clinical trial on humans are projected to occur within the next several years. In the meantime, Dr. Khalili will conduct follow-up studies in a larger group of animals, in which the researchers plan to monitor for effects of the treatment, its safety, and other important indices.
Other researchers contributing to the study include Rafal Kaminski, Chaoran Yin, Jessica Otte,Jennifer Gordon, and Wenhui Hu, Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University; Ramona Bella and Pasquale Ferrante, Microbiology and Clinical Microbiology, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Howard E. Gendelman, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center; and Hailong Li and Rosemarie Booze, Behavioral Neuroscience, Department of Psychology, University of South Carolina.
Full disclosure: Drs. Khalili, Hu, and Kaminski hold the patents that cover the viral gene editing technology. Dr. Khalili is a co-founder, board member, scientific advisor, and holds equity in Excision Biotherapeutics, a biotech start-up which has licensed the viral gene editing technology from Temple University for commercial development and clinical trials.