In a few months, Penn researchers may simultaneously transform HIV treatment and the entire technology of gene therapy.
Researchers are submitting a proposal to the Federal Drug Administration for approval to test in humans, for the first time, a new protein specially engineered to create HIV-resistant immune cells.
The protein - called a "zinc finger nuclease" - is designed to suppress the gene that creates the site through which the HIV virus enters certain immune cells.
According to Pathology and Laboratory Medicine professor Bruce Levine, a member of the Penn team developing the therapy, the gene is naturally absent in about 1 percent of humans. They are immune to HIV as a result.
Yet aside from the technology's potential as an HIV treatment, pharmacologists and bioengineers across the country are excited about the first-ever human trial of the therapy.
"Those of us who work with zinc fingers are very interested in the outcome of this trial," David Segal, a professor at the University of California at Davis Genome Center who is unaffiliated with the Penn research, said. "To some extent, we all rise and fall with the results."
Unlike traditional gene therapies, which insert therapeutic genes into unhealthy cells to heal them, zinc finger nucleases make permanent changes to the cells' DNA.
Inserting foreign genes into a cell can affect cell functions in unexpected, unhealthy ways, Segal said.
Most notoriously, the gene therapy with which researchers tried to cure Severe Combined Immunodeficiency Disease - also known as "bubble boy disease" - ended up causing cancer in human test subjects.
Zinc finger treatment is less likely to run into those problems, Elena Perez, professor of Pediatrics at the Children's Hospital of Philadelphia and the lead researcher on the project, said.
Like traditional gene therapy, however, a zinc finger nuclease treatment would only modify a tiny percentage of immune cells, equipping those cells with what Levine calls "a survival advantage."
This advantage is apparent in laboratory tests. After mixing zinc-finger-treated cells with untreated cells and the HIV virus in a petri dish, Perez said, the treated cells became dominant after 60 or 70 days.
But enhancing cell resistance to HIV with zinc finger nucleases is not tantamount to vaccinating an individual against the virus, Levine said.
"This isn't something that we want to promise as a cure, but as a treatment," he said. "It's something that would allow people to live with a chronic disease in a healthier way, insusceptible to the debilitating infections that people with advanced HIV have."
