Video: A breakthrough at Temple University brings HIV researchers closer to treatment | Health

Dr. Hariri is a senior collaborator in new research Tricia H. Burdo, PhD, Associate Professor and Vice-Chair of Education, Department of Neuroscience, LKSOM. Experts in the use of SIV (simian immunodeficiency virus) infection antiretroviral therapy (ART) treatment rhesus monkey models for HIV etiology and treatment studies.When Dr. Andrew G. McLean, Associate Professor of Tulane National Center for Primate Research and Department of Microbiology and Immunology, Tulane University School of Medicine, Dr. Bin Farin, Associate Professor, Southwestern National Primates Research Center, Texas Biomedical Institute. Dr. Lin was previously an associate professor at the Tulane National Center for Primate Studies and a Department of Microbiology and Immunology at Tulane University School of Medicine. Dr. Pietro ManxoDr. Hariri’s lab assistant scientist at LKSOM’s Department of Neuroscience was the first author of the report. Published in the journal online on November 27 Nature Communications..

Of particular importance, new studies show that the gene-editing construct developed by Dr. Hariri’s team can reach infected cells and tissues known as virus reservoirs for SIV and HIV. These reservoirs are cells and tissues in which the virus integrates into the host DNA and hides for years, providing a major barrier to curing the infection. SIV or HIV in these reservoirs is beyond the scope of ART, which suppresses virus replication and removes the virus from the blood. As soon as ART stops, the virus emerges from the reservoir and updates the replication.

In non-human primates, SIV behaves very much like HIV. “The SIV-infected rhesus monkey model studied in Dr. Burd’s lab is an ideal large animal model for reproducing human HIV infection,” explained Dr. Hariri.

In the new study, researchers began by designing an SIV-specific CRISPR-Cas9 gene editing construct. Experiments in cell culture confirmed that editing tool-integrated SIV DNA was cleaved from host cell DNA in place, limiting the risk of potentially harmful gene editing at off-target sites. It was. The research team then packaged the construct on an adeno-associated virus 9 (AAV9) carrier that can be injected intravenously into SIV-infected animals.

Dr. Burdo, in collaboration with colleagues at the Tulane National Primate Research Center, randomly selected three SIV-infected macaques, each injected once with AAV9-CRISPR-Cas9 and used as a control in another animal. Did. Three weeks later, the researchers took blood and tissue from the animals. Analysis showed that in AAV9-CRISPR-Cas9-treated macaque, the gene-editing construct was distributed over a wide range of tissues, including bone marrow, lymph nodes, and spleen, and reached CD4 + T cells. Virus reservoir.

In addition, Temple researchers have demonstrated that the SIV genome is effectively cleaved from infected cells, based on genetic analysis of treated animal tissues. “Step-by-step excision of SIV DNA was done with high efficiency from tissues and blood cells,” explained Dr. Mancuso. Resection efficiency varies from tissue to tissue, but has reached particularly high levels in the lymph nodes.

A new study, Dr. Khalili and colleagues to develop a new gene editing system using CRISPR-Cas9 technology (the subject of the 2020 Nobel Chemistry Awards) to specifically remove HIV DNA from viral-containing genomes It is a continuation of efforts by. Researchers have previously shown that their system can effectively eliminate HIV DNA from cells and tissues of HIV-infected small animal models, including HIV-1 humanized mice.

Co-author Dr. McLean is encouraged by the findings. “This is an important development that we hope to put an end to HIV / AIDS,” says MacLean. “The next step is to evaluate this treatment over time to determine if the virus can be completely eliminated. Perhaps you can even remove the subject from ART.”

Dr. McLean hopes that this treatment strategy will lead to population. Excision BioTherapeutics, a biotechnology company with Dr. Khalili as scientific founder, Dr. Burdo as a contributor to preclinical research and development, and a scientific advisory board, has funded large-scale post-approval research and future clinical trials. And support the infrastructure. According to the Food and Drug Administration.

“We want to move our work to human clinical research soon,” added Dr. Khalili. “People around the world have been suffering from HIV for 40 years and are very close to clinical research that could lead to the treatment of HIV infection.”

Other researchers contributing to the research are: Chen Chen, Dr. Rafal Kaminsky, Dr. Jennifer Gordon, Dr. Schlenryao, Jake A. Robinson, Mandy D. Smith, Dr. Hong Liu, Dr. Ilkar K. Sarier, Rahsan Sariyer,and Dr. Martina Donadni, Temple University, Luis Katz School of Medicine, Center for Neurovirology, Department of Neuroscience; Slow Dr. Tiffany A. Peterson, Jacqueline B. Williams,and Summer Sidiki, Comparative Pathology Division, Primate Research Institute, Tulain.And Dr. Bruce A. Bunnell, Tulane National Primate Research Center, Tulane Brain Institute, Tulane University School of Medicine, Department of Pharmacology, and Fort Worth’s North Texas University Health Science Center, Department of Microbiology, Immunology, and Genetics.