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T cells get tough against HIV: in mice, RNA 'scissors' keep the AIDS virus at bay.

I pity the fool who messes with these T cells.

Delivering molecular "scissors" into T cells in mice makes the immune cells downright hostile to HIV. Not only do the cells reject the virus's advances, but copies of the virus already inside the cells get snipped up.

The technique is the first to deliver these HIV-fighting scissors--called small interfering RNAs, or siRNAs--into T cells in living animals, Premlata Shankar of Texas Tech University Health Sciences Center in E1 Paso and her colleagues report in the Aug. 22 Cell.

"They've shown very nicely that you can ... target T cells and knock down the virus," comments John Rossi, an AIDS researcher at City of Hope's Beckman Research Institute in Duarte, Calif. "It's a nice proof of principle that I think could be developed into a viable therapy."

Previous research on cells in lab dishes showed that customized siRNAs can snip the molecules that enable HIV to enter and kill T cells. Ceil death leads to the immune deficiencies characteristic of AIDS. In the new experiments, done when Shankar was at Harvard Medical School, custom siRNAs were injected into mice that had their blood cells replaced with human ones. The siRNAs prevented T cell loss.

"It could become a very good adjunct therapy," Shankar says.

Existing drugs also inhibit HIV from replicating inside T cells. But unlike those drugs, siRNAs can be quickly modified to target viral mutations that make HIV resistant to conventional drugs.

An siRNA is a short molecule only 20 to 25 "letters" of genetic code long. If that code matches up with a gene segment, the siRNA blocks production of the protein encoded by that gene. Shankar's team used an siRNA that targets the gene for a protein called CCR5, which sits on the surface ofT cells. To enter the cells, most HIV variants first bind to CCR5, so blocking its production slams the door on HIV.

The researchers delivered this siRNA, along with two others that target the genetic code of the virus itself, by coupling the molecules to an antibody that binds to a protein on the T cell surface.

More research to check for toxicity is needed, Rossi says. Further tests on monkeys are also needed before the treatment can be tested in human clinical trials.
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Title Annotation:Genes & Cells
Author:Barry, Patrick
Publication:Science News
Geographic Code:1USA
Date:Aug 30, 2008
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