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Gene Silencing May Stop AIDS Virus

Study Shows New Technique Has Potential as AIDS Therapy
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Fischl has seen a lot of promising AIDS therapies come and go, but she finds the siRNA approach "intriguing" and would like to see it explored further.

One of the researchers doing this exploration is Ramesh K. Akkina, PhD, professor of microbiology, immunology, and pathology at Colorado State University, Fort Collins.

"The Shankar lab's finding is certainly an exciting development," Akkina tells WebMD. "This siRNA is a very interesting molecule that is actually programming cells to deal with the virus."

Akkina notes that the Shankar/Kumar team is using direct injections of siRNA constructs, an approach to gene therapy that would require repeat administrations. Another approach uses a genetically engineered virus that infects blood-forming stem cells and becomes a permanent part of their genome. When these stem cells become T cells, they produce siRNA and are immune to HIV infection.

"In the approach with the stem-cell gene-therapy approach, we are programming blood-forming stem cells with anti-HIV siRNA so that the stem cells are viable lifelong in the individual," Akkina says. "The virus-resisting cells are produced on a daily basis."

Sponsored by Benitec, the firm developing this approach, a phase I safety study of virus-delivered siRNA is under way at City of Hope Medical Center in Duarte, Calif.

Kumar says her team's approach would avoid the pitfall of having a foreign virus integrate into the human genome.

Both approaches hold promise for reaching the so-called "resting" T-cells in which HIV is able to hide from current AIDS therapies. Reaching these HIV reservoirs is the key to eliminating HIV from the body.

"These approaches could be used to purge the latently infected cells," Akkina says.

Kumar agrees.

"The advantage of siRNA is that you can deliver it into resting T cells," she says. "So if these siRNA are present when the cell becomes activated and starts to produce HIV, you have siRNA there ready to combat it."

Kumar and colleagues report their findings in the Aug. 22 issue of the journal Cell. Kumar, an instructor at Harvard Medical School while working in the Shankar lab, is now an assistant professor at Yale University.

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