The Proceedings of the National Academy of Sciences USA reported online that researchers at the University of California-Los Angeles and the California Institute of Technology have developed a new gene therapy approach that prevents the AIDS virus from entering human cells. The technique offers a potential way to treat HIV patients and holds implications for treating any disease caused by a gene malfunction, including cancer.

The investigative team devised a new application for a genetic technology called small interfering RNA (siRNA). The synthetically designed siRNAs act as a catalyst to reduce the expression of specific genes and to slow the progression of disease.

"Synthetic siRNAs are powerful tools, but scientists have been baffled at how to insert them into the immune system in stable form," explained Dr. Irvin S.Y. Chen, director of the UCLA AIDS Institute. "You can't just sprinkle them on the cells. Our research is the first to create a delivery system using a vehicle derived from HIV itself. This system allowed us to introduce the siRNAs into the cell, where they can protect against HIV infection."

Chen collaborated with Dr. David Baltimore, Nobel laureate, president of Caltech and a professor of biology there. They worked closely with Dr. Don Sung An and Dr. Xioa-Feng Qin to construct a carrier from a disarmed version of HIV to deliver siRNAs into human cells. HIV requires two receptors to penetrate a cell, according to Baltimore. One is CD4, a T-cell essential for immune function. The other is CCR5, which plays a role in immune function but is not necessary for normal body function. In fact, roughly 1 percent of Caucasians are born without CCR5, and large studies have shown that this population is naturally protected from HIV infection.

The researchers cultured T-cells from healthy people's blood and inserted siRNAs into the cells. Then they introduced HIV and incubated the culture for eight days, repeating the experiment four times for accuracy. When they examined the culture, the scientists saw a 10-fold drop in CCR5 expression. HIV had managed to infect fewer than 20 percent of the cells; the rest were protected.

"Our findings raise the hope that we can use this approach or combine it with drugs to treat HIV in people -- particularly in persons who have not experienced good results with other forms of treatment," noted Baltimore. Now that scientists can introduce siRNAs into the cell, Chen and Baltimore proposed that the technology will become a major therapeutic approach for many diseases in the future, including infectious, autoimmune and immunological diseases.

The full report, "Inhibiting HIV-1 Infection in Human T Cells by Lentiviral-Mediated Delivery of Small Interfering RNA Against CCR5," was published in the Proceedings of the National Academy of Sciences USA (2003;100:183-188; published online before print as 10.1073/pnas.232688199).

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