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Gene Silencing May Stop AIDS Virus

Study Shows New Technique Has Potential as AIDS Therapy
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WebMD Health News
Reviewed by Louise Chang, MD

Aug. 8, 2008 -- A new gene silencing technique stops HIV cold in mouse studies and promises to become a potent new AIDS therapy with few side effects.

The technique uses short interfering RNA, also called silencing RNA or siRNA. These tiny snips of RNA are designed to stick to specific genes, which are then rendered inoperative or "silent."

Researchers have previously shown that siRNA aimed at HIV can shut down the AIDS virus in the test tube. It can also target the T cells HIV loves to infect, shutting the window through which HIV enters.

Now Priti Kumar, PhD, Premlata Shankar, MD, and colleagues have linked siRNA to an antibody that delivers them directly to T cells -- and to a molecule that transports them to the cell nucleus where it can attack HIV genes.

They used a siRNA cocktail: two siRNAs that inactivate different HIV genes and one siRNA that keeps T cells from expressing the CCR5 molecule to which HIV attaches.

"In mice pre-treated with the siRNA cocktail and then infected with HIV, we could not find any signs of virus for a long period of time," Kumar tells WebMD. "And when we treated mice whose immune systems had been reconstituted with T cells from an HIV infected individuals, they were totally able to block expansion of the virus."

Working in Shankar's Harvard lab (recently moved to the Texas Tech Health Sciences Center), the researchers used recently developed mouse models of HIV infection. In these models, immune-deficient mice have their immune systems reconstituted either with adult human T cells or with human stem cells that provide a continuing source of T cells.

"You get a mouse with the immune system of a human," Kumar says.

This mouse model is a big advance in the development of new AIDS treatments, says longtime AIDS researcher Margaret Fischl, MD, director and principal investigator of the AIDS clinical research unit at the University of Miami.

"The humanized mouse model is very interesting," Fischl says. "It would give me much more information on the effectiveness and toxicity of treatments and save time in human clinical trials."

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