Gene Silencing May Stop AIDS Virus
Study Shows New Technique Has Potential as AIDS Therapy
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
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
"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."
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
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