Researchers study HIV immunity

With about 2.1 million adults infected worldwide in 2007 alone, HIV - the virus that causes AIDS - is the focus of research across the globe. Researchers at Penn have joined the many involved with efforts that may lead to a decrease in the rate of infection.

Carl June, Elena Perez and their colleagues are conducting research at the Penn Abramson Family Cancer Research Institute and the Sangamo Biosciences Laboratary in Richmond, Calif., to determine whether it is possible to create large-scale immunity against HIV through the use of naturally occurring proteins called zinc fingers.

An autoimmune virus, HIV infects immune cells such as T-cells - one of the two major types of white blood cells in the body. These cells are crucial in the body's ability to fight infection and disease. In the case of an HIV infection, the body will have a weakened ability to fight infection.

To gain entry into these cells, most strains of the virus bind to CCR5 receptors. Some people, however, are born with a mutation that causes a non-functional CCR5 receptor. This makes them immune to HIV infection.

"The few people born entirely without [the CCR5 gene] (about 1% of Caucasians, fewer of other races) are well protected against AIDS," wrote John James, editor and publisher of AIDS Treatment News in an e-mail.

In their research, June and his colleagues are trying to artificially reproduce this immunity. They engineered zinc fingers - which naturally bind to DNA sequences - to bind to the CCR5 gene and bring a DNA enzyme that cuts a portion of the gene sequence. Left without the CCR5 gene, it is nearly impossible for HIV to penetrate the T-cells.

The tests have been conducted on T-cells of mice, rather than humans, by injecting the mice with T-cells that had been modified using the engineered zinc fingers.

Whether or not this procedure would work well in humans is uncertain.

The Phase I clinical trials will be conducted on human patients later this year, said Perez.

While the research could be a monumental discovery, not everyone is ready to celebrate just yet.

"This gene technology could be very important in the long term, for various diseases. But development will take time," wrote James. "No one is holding their breath for immediate relief."

With millions of people contracting the disease annually, AIDS treatment is extremely expensive and unavailable in many parts of the world. Perez said that researchers need to strive for new and better therapies that are also accessible to patients worldwide.

"This work will lead to new ways of thinking about HIV treatment," she wrote in an e-mail. "And possibly a better understanding of the disease."

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