Summary of Gene Therapy Can Effectively Eliminate HIV Infection:
Researchers from Temple University and the University of Nebraska Medical Center have published a study in the Proceedings of the National Academy of Sciences demonstrating that gene-editing combined with antiretroviral medications has successfully cured animals of HIV-1, the virus responsible for AIDS. HIV is a virus that attacks the immune system, making it difficult for the body to fight off infections and diseases. It is primarily transmitted through sexual contact, sharing of needles, or from mother to child during pregnancy, childbirth, or breastfeeding. The dual gene-editing strategy holds exceptional promise for treating HIV in humans as it is a simple and relatively inexpensive approach. The researchers plan to test the system on non-human primates soon.
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Gene-Editing Therapy Successfully Eradicates HIV in Animal Models: A Breakthrough in HIV Treatment
Human Immunodeficiency Virus (HIV) is a virus that attacks the immune system, making it difficult for the body to fight off infections and diseases. HIV is primarily transmitted through sexual contact, sharing of needles, or from mother to child during pregnancy, childbirth, or breastfeeding. If left untreated, HIV can progress to acquired immunodeficiency syndrome (AIDS), which can be fatal.
Researchers from Temple University and UNMC collaborate in a study recently published in the journal Proceedings of the National Academy of Sciences. Gene-editing therapy targeting both HIV-1, the virus responsible for AIDS, and CCR5, the co-receptor assisting viral entry into cells, has been demonstrated to eradicate HIV infection, according to new research effectively.
Cutting-Edge Dual Gene-Editing Approach
The study, published in the journal Proceedings of the National Academy of Sciences (PNAS), marks the first instance of combining a dual gene-editing approach with antiretroviral medications to cure animals of HIV-1 successfully.
“The idea to bring together the excision of HIV-1 DNA with inactivation of CCR5 using gene-editing technology builds on observations from reported cures in human HIV patients,” said Kamel Khalili, Ph.D., Laura H. Carnell Professor and Chair of the Department of Microbiology, Immunology, and Inflammation, Director of the Center for Neurovirology and Gene Editing.
Collaborative Research
Dr. Khalili and Howard E. Gendelman, MD, Professor and Chair of the Department of Pharmacology and Experiential Neuroscience at UNMC, were senior investigators in the new study. The two researchers have been long-time collaborators and have strategically combined their research strengths to find a cure for HIV.
“We are true partners, and what we achieved here is spectacular,” Dr. Gendelman said.
Previous Work
In previous work, Drs. Khalili, Gendelman, and their respective teams showed that HIV could be edited out from the genomes of life, humanized HIV-infected mice, leading to a cure in some animals. For that research, Dr. Khalili and co-investigator Rafal Kaminski, Ph.D., Assistant Professor at the Center for Neurovirology and Gene Editing at the Katz School of Medicine, combined their expertise in CRISPR gene-editing technology for targeting HIV-1 with a therapeutic strategy known as long-acting slow-effective release (LASER) antiretroviral therapy (ART) that was co-developed by Dr. Gendelman and Benson Edagwa, Ph.D.
Challenges and Solutions
Despite being able to eliminate HIV in LASER-ART mice, researchers found that HIV could eventually re-emerge from tissue reservoirs and cause rebound infection. This effect is similar to rebound infection in human patients who have been taking ART but suddenly stop or experience a disruption in treatment.
To prevent rebound infection, Dr. Khalili’s team began work on next-generation CRISPR technology for HIV excision, developing a new, dual system to eliminate HIV from the animal model permanently. Experimental results show that the developed CRISPR gene-editing constructs, when administered together, resulted in viral suppression, restoration of human T-cells, and elimination of replicating HIV-1 in 58% of infected animals.
A Promising Future
The Temple team also anticipates testing the dual gene-editing strategy in non-human primates. The new dual CRISPR gene-editing strategy holds exceptional promise for treating HIV in humans. “It is a simple and relatively inexpensive approach,” Dr. Khalili noted. “Curing HIV is the big picture,” Dr. Gendelman added. “Through our ongoing collaboration, Temple and UNMC have carried out meaningful research that could ultimately impact many people’s lives.”
The National Institutes of Health funded the study. Researchers from both universities have an interest in commercializing their discovery.
