Study published in Nature Communications marks a critical step toward the development of a possible cure for human HIV infection

San Francisco, CA, Nov. 30, 2020 (GLOBE NEWSWIRE) -- Taking a major step forward in HIV research, scientists at the Lewis Katz School of Medicine at Temple University have successfully edited SIV – a virus closely related to HIV, the cause of AIDS – from the genomes of non-human primates. The breakthrough, reported in the journal Nature Communications, marks a critical step toward the development of a possible cure for human HIV infection. Excision BioTherapeutics holds the exclusive license for commercial application of these advancements as it works on the development and commercialization of advanced gene editing therapeutics for the treatment of life-threatening diseases caused by viruses.

“For the first time, a single inoculation of our CRISPR gene-editing construct, carried by an adeno-associated virus, can edit out the SIV genome from infected cells in rhesus macaque monkeys,” said 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) and the Co-Founder and Chief Scientific Consultant to Excision.

Of particular significance, the new work shows that the gene-editing construct can reach infected cells and tissues known to be viral reservoirs for SIV and HIV. These reservoirs, which are cells and tissues where the viruses integrate into host DNA cause the virus to emerge as soon as antiretroviral therapy (ART) is stopped.

Dr. Tricia Burdo, Associate Professor and Associate Chair of Education in the Department of Neuroscience at the Lewis Katz School of Medicine at Temple University, and Scientific Advisory Board member to Excision added, “The SIV-infected rhesus macaque model is an ideal large animal model for recapitulating HIV infection in humans.”

For the new study, the researchers began by designing an SIV-specific CRISPR-Cas9 gene-editing construct. Experiments in cell culture confirmed that the editing tool cleaved integrated SIV DNA at the correct location from host cell DNA, with limited risk of potentially harmful gene editing at off-target sites. The research team then packaged the construct into an adeno-associated virus 9 (AAV9) carrier, which could be injected intravenously into SIV-infected animals. Analyses showed that in AAV9-CRISPR-Cas9-treated macaques, the gene-editing construct had been distributed to a broad range of tissues, including the bone marrow, lymph nodes, and spleen, and had reached CD4+ T cells, and that the SIV genome was effectively cleaved from infected cells.

The new study is a continuation of efforts by Dr. Khalili, Dr. Burdo, and colleagues to develop a novel gene-editing system using CRISPR-Cas9 technology – the subject of the 2020 Nobel Prize in Chemistry – to specifically remove HIV DNA from genomes harboring the virus. The researchers have shown previously that their system can effectively eliminate HIV DNA from cells and tissues in HIV-infected small animal models, including HIV-1 humanized mice.

“This work is a critical step to initiating human clinical studies for a cure to HIV,” stated Daniel Dornbusch, CEO of Excision. “Researchers have searched for a cure for viruses such as HIV for decades. This important work brings us a step closer to evaluating the safety and efficacy of a single infusion to cure infected people around the world. We are proud of the team’s diligent work and effort and look forward to progressing this important product to human clinical trials.”

This press release was announced in GlobeNewsWire: http://www.globenewswire.com/news-release/2020/11/30/2136855/0/en/HIV-Like-Virus-Eliminated-from-the-Genomes-of-Primates-Excision-BioTherapeutics-Advancing-the-Innovation-to-Clinical-Development.html