Genetics Could Hold Secret to AIDS Cure

There's a genetic hijacker on the loose, and its name is HIV.

The virus attacks by injecting a single strand of genetic material into the body's cells, then borrows a person's own gene replication mechanisms to make thousands of copies of itself.

But AIDS researchers have been cooking up their own genetic wizardry to outwit this killer. This week, at the 13th International AIDS conference in Durban, South Africa, one team of experts will present their latest genetic designs for halting the virus: a genetically engineered vaccine that helps boost the immune system.

Developed by Drs. Franco Lori and Julianna Lisziewicz of the Research Institute for Genetic and Human Therapy in Washington, D.C., the plan involves genetically modified immune system stem cells that produce T-cells that resist the HIV virus. The group has already tried the vaccine successfully on animals and is now preparing for trials on humans.

"We think this is a unique vaccine," Lisziewicz said. "We have never seen such a T-cell response in the animal model."

HIV typically attacks the body's immune system and wipes out the T-cells, the immune system's disease-fighting cells. By making T-cells immune, the vaccine can counteract the deadly effects of HIV. This would make it more than a vaccine — it's a potential cure for people who already have early-stage HIV.

The genetically engineered vaccine is different from the numerous other vaccines in development for HIV. While these other vaccines follow the classic vaccine model — inject someone with a killed virus or a portion of a killed virus to produce antibodies — this vaccine is designed to power up the body's immune system cells.

The "T-cell immunity" that Lori and Lisziewicz hope to induce with their vaccine is the same response they observed in a now-famous HIV case known as "the Berlin patient." This patient began a regimen of anti-HIV drugs soon after becoming infected with the virus, then stopped medication on his own and discovered that his immune system bounced back. In the few years since, no HIV has been detected in his system even though he is off the medication.

Doctors have been puzzling over why this patient seems to have been "cured" or at least had the clock stopped temporarily on the ticking time bomb inside of him. If Lisziewicz and Lori can induce this change with a vaccine, they may learn the precise mechanism by which this patient has had his disease arrested.

Lisziewicz says her team is developing initial human trials of their vaccine. These trials will determine whether the vaccine is safe. They don't expect to have difficulty with toxicity.

Attacking HIV Genes

Lori and Lisziewicz have also experimented with a more direct tactic for genetically foiling HIV: They have introduced genes into the cells that directly interfere with the HIV genes "tat" and "rev," sequences of chemical letters that direct HIV to perform certain tasks. Tat helps the deadly HIV sequences to copy themselves; rev helps them get into other cells and infect them.

Recently, Lisziewicz discovered a gene that inhibits expression of both of these HIV genes. "The beauty of this gene is that it is only expressed in cells infected with HIV," she said. "In normal cells it is silent." This means the gene could safely be inserted into all of the body's cells to stop HIV from genetically hijacking cells it has infected.

Scientists have not yet been able to use this gene in clinical human trials, but the T-cell vaccine holds promise for halting the spread of HIV. The technology of gene therapy — for HIV or other conditions — remains just out of reach as a practical treatment.