Groundbreaking Research From Temple U Could Lead to Cure for AIDS

Local researchers announced a major step forward in the battle against AIDS and the HIV virus. Researchers successfully eliminated the HIV virus from cultured human cells for the first time, according to Temple Health.

"This is one important step on the path toward a permanent cure for AIDS," says Kamel Khalili, PhD, Professor and Chair of the Department of Neuroscience at Temple. “It’s an exciting discovery, but it’s not yet ready to go into the clinic. It’s a proof of concept that we’re moving in the right direction.”

Dr. Khalili along with his colleague, Wenhui Hu, MD, PhD, the Associate Professor of Neuroscience at Temple, led the groundbreaking research, which was funded by grants from the National Institutes of Health. Khalili and his team created molecular tools to delete the HIV-1 proviral DNA. They used a combination of DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA(gRNA) to hunt down the viral genome and excise the HIV-1 DNA. The process allowed the cell’s gene repair machinery to take over, soldering the loose ends of the genome back together leading to virus-free cells.

"Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease," says Khalili.

Khalili’s lab engineered a 20-nucleotide strand of gRNA to target the HIV-1 DNA and paired it with Cas9. The gRNA targets the control region of the gene known as the long terminal repeat(LTR) which are present on both ends of the HIV-1 genome. The Cas9 nuclease can snip out the 9,709 nucleotides that comprise the HIV-1 genome.

The process was successful in several cell types that can harbor HIV-1.

“T-cells and monocytic cells are the main cell types infected by HIV-1, so they are the most important targets for this technology,” Khalili said.

Over the last 15 years, doctors have used highly active antiretroviral therapy (HAART) to control HIV-1 for infected people in the developed world. However, HAART can’t prevent the virus from raging again during an interruption in treatment. HIV-1 replication can also still have health consequences even when it’s under control.

“The low level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with aging,” Khalili says. “These problems are often exacerbated by the toxic drugs that must be taken to control the virus.”

The problems include the weakening of the heart muscle, bone disease, kidney disease and neurocognitive disorders.

Khalili says the new process he and his team developed faces several challenges before its ready for patients. The team must come up with a way to deliver the therapeutic agent to every infected cell. Khalili also says treatment may have to be individualized for each patient’s unique viral sequences since HIV-1 is prone to mutations.

"We are working on a number of strategies so we can take the construct into preclinical studies,” Khalili says.  “We want to eradicate every single copy of HIV-1 from the patient.  That will cure AIDS.  I think this technology is the way we can do it.”

Khalili also says the same technique could theoretically be used against other viruses.

More than 33 million people have HIV worldwide and more than 1 million in the United States. Every year, another 50,000 Americans contract the virus, according to the U.S. Centers for Disease Control.

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