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May 03, 2023

In the search for an HIV cure, a new gene-editing strategy from Temple scientists may be a game-changer

Targeting the virus and the molecule that helps it invade cells can eliminate HIV from the body, researchers say. Their findings are based on a study on mice

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Temple HIV Research Thom Carroll/For PhillyVoice

Temple University researchers say HIV can be eliminated from the body by using a new gene-editing approach in combination with an antiretroviral therapy. Their findings are based on a study on mice.

Scientists at Temple University say they have gotten closer to a cure for HIV by combining a new gene editing therapy with antiretroviral drugs. 

The researchers say the human immunodeficiency virus can be effectively eliminated from the body by using a gene-editing strategy that targets the virus and the molecule that helps the virus invade cells. They say this strategy has a lot of promise because it is simpler and less expensive than the approach used in the few times that people have been cured of HIV.

"The type of bone marrow transplant that has brought about cures in humans is reserved for patients who also have leukemia," said Kamel Khalili, who directs both Temple's Center for Neurovirology and Gene Editing and the Comprehensive NeuroAIDS Center. "It requires multiple rounds of radiation and is not applicable in resource-limited regions, where HIV infection tends to be most common."

HIV targets the body's immune cells, which help fight off infections. HIV can be controlled with the use of antiretroviral therapy, but when the medication is stopped, it eventually turns into AIDS.

An estimated 1.2 million U.S. residents had HIV at the end of 2019, the most recent data available, according to the U.S. Centers for Disease Control and Prevention. Another 30,635 people were diagnosed in 2020. 

In the last decade, scientists have been exploring how the gene editing tool CRISPR-Cas9 can be used to eliminate an HIV infection. The therapy typically targets just the virus, but the research conducted by the Temple scientists and others at the University of Nebraska Medical Center may change that.

Their study, published in The Proceedings of the National Academy of Sciences, was the first to combine a dual gene-editing therapy with antiretroviral drugs to cure HIV in animals.

The researchers were inspired to explore the potential benefits of inactivating the co-receptor CCR5, a molecule that allows HIV to enter cells, after reading about reported cures in HIV patients. 

"In the few instances of HIV cures in humans, the patients underwent bone marrow transplantation for leukemia, and the donor cells that were used carried inactivating CCR5 mutations," he said.

Temple HIV research teamCourtesy/Temple University

Temple University researchers say HIV can be effectively eliminated from the body by targeting the virus and the molecule that helps the virus invade cells.

Khalili collaborated with Dr. Howard E. Gendelman, who chairs the Department of Pharmacology and Experiential Neuroscience at the University of Nebraska Medical Center, on the study. The pair has worked together for years. 

The Temple scientists generated gene-editing constructs that were applied to lab mice receiving an antiretroviral therapy developed by the Nebraska researchers. They determined when to administer gene-editing therapy and how to best excise HIV, inactive CCR5 and suppress viral growth, Gendelman said. 

Previous research among the scientists has shown HIV can be edited out of the genes of HIV-infected mice. Some of the animals were completely cured. In that research, they combined CRISPR gene-editing technology with a long-acting antiretroviral therapy. The slow release of the medication made it possible to limit HIV from replicating, even at a less frequent dose.

Their latest work used next-generation CRISPR technology that focused on both HIV excision and CCR5 inactivation. Khalili and his team developed a simple procedure for CCR5 inactivation that administers the CRISPR gene editing molecule through an IV.

"From success stories of human HIV patients who have undergone bone marrow transplantation for leukemia and been cured of HIV, our hypothesis was that the loss of the virus's receptor, CCR5, is important to permanently eliminating HIV infection," Khalili explained.

The Nebraska scientists tested Temple's dual technology on mice also receiving an antiretroviral therapy. They found the dual gene-editing therapy effectively suppressed HIV, restored immune cells, and prevented HIV from replicating in 58% of the infected animals. 

The Temple researchers next seek to test the gene-editing strategy on lab primates. 

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