Philly Native, Iranian Immigrant Eliminate HIV in Mice

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Kamel Khalili and Howard Gendelman
From left: Kamel Khalili and Howard Gendelman (Photo by Soffia Gendelman)

A new treatment has eliminated HIV in mice, according to a study published earlier this month in Nature Communications.

The treatment works by tackling the virus on two fronts, by both suppressing and eliminating it, in mice with humanized immune systems.

Behind the study were two teams of researchers led by Howard E. Gendelman, chair of the department of pharmacology and experimental neuroscience at the University of Nebraska Medical Center, and Kamel Khalili, director of the Center for Neurovirology and director of the Comprehensive NeuroAIDS Center at Temple University’s Lewis Katz School of Medicine. Both had spent years working on different technologies to tackle HIV, yet only by bringing their research together was this milestone possible.

Now, not only are they colleagues, but Gendelman, born and raised Jewish in Northeast Philly, and Khalili, who immigrated from Tehran shortly after the Iranian Revolution, consider themselves good friends.

In fact, Khalili said, “we upgraded ourselves to brothers.”

But neither would say they got along when they first met more than 30 years ago, as early-career scientists studying HIV/AIDS at the National Institutes of Health.

In the early ’80s, HIV didn’t even have a name yet, said Gendelman, the Margaret R. Larson professor of internal medicine and infectious diseases. By the end of the decade, more than 89,000 people would die from AIDS in the United States, according to amfAR, The Foundation for AIDS Research.

Despite the common cause of their work, their different backgrounds created somewhat of a culture clash between them. As Gendelman put it, they “ran hot and cold.”

“We were very competitive with each other,” said Khalili, the Laura H. Carnell professor and chair of the department of neuroscience, “but once we worked with each other, we found each other very, very similar in many ways, but the goal obviously was … to accomplish something which could put an end to the disease, which has been with us for many years. Through this collaboration, we found each other also as a good friend and obviously, as friendships goes, way beyond laboratories right now.”

They would each go on to spend much of their careers focused on the disease, though their work took them in different directions. Gendelman wound up working with long-acting slow-effective release antiretroviral therapy, also called LASER ART, in Nebraska, while Khalili worked at a variety of institutions in Philadelphia, eventually landing at Temple, where he has been trying to use CRISPR-Cas9 to eliminate the viral genome from the infected cells.

About four years ago, the two realized they would be far more successful working together, and they pooled their research.

That’s how a Jewish Philadelphia native and an Iranian immigrant wound up eliminating HIV in mice. They emphasized that it’s just the beginning of what they hope will eventually lead to a cure for humans.

“Science doesn’t know religion and ethnic origins,” said Gendelman, a recipient of the Jewish Federation of Omaha Humanitarian of the Year Award. “It just knows alleviating suffering. It breaks down boundaries. There’s nothing bad; it’s not like making weapons. You’re actually doing something that changes humanity for the better. That’s why I think it’s a cool way to bring people together.”

By combining LASER ART, which could suppress HIV, and CRISPR-Cas9, which could eliminate the virus, they thought they could attack HIV on two fronts and arrive at a cure, Khalili said.

The next step is to optimize their method and make it safer and more potent. They have already begun primate studies. They hope clinical trials will follow.

“We demonstrated for the first time that a cure might be possible,” Khalili explained. “Since the AIDS epidemic in the early ’80s, no one thought that they can cure it. They can treat it with antiretroviral treatments, but they can’t cure it. The cure comes from the complete elimination, which this CRISPR technology seems to be able to do that, but it cannot do that by itself. It needs to have a potent antiretroviral inhibitor.”

Gendelman credits his mother with the friendship between the two scientists. She suggested they invite Khalili over, and she made him a part of their extended family. He was the only non-family member at her 90th birthday party, and Khalili was the first person to visit her when she was out of the intensive care unit with cancer, Gendelman said.

“She was the glue,” Gendelman said. “She made it family, rather than just curing HIV. He became an extended part of my family in Philadelphia.”

Now, Gendelman and Khalili talk multiple times a week, and when Gendelman comes to Philly once every other month, he makes time to see Khalili. The two always catch up over bagels and lox — Khalili’s favorite breakfast food — from Hymie’s Delicatessen. They’ve also been to Israel together.

“Our relationship was much more than science, which made science a lot easier,” Gendelman said. “If you like the people you’re working with, it’s a lot easier to do great things.”

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