A new method of targeting the virus that causes AIDS may provide a powerful one-two punch against the disease, according to a Jan. 19 report in the journal Science Translational Medicine. The findings could improve HIV-positive patients’ chances of overcoming the infection.
|John Rossi leads research aimed at defending HIV-positive patients from the virus. (Photo by Paula Myers)|
Scientists led by John J. Rossi, Ph.D., chair of the Department of Molecular and Cellular Biology and Lidow Family Research Chair, developed a small piece of genetic material — called an RNA aptamer — that both interferes with HIV’s ability to infect cells and acts as a delivery vehicle for another anti-HIV molecule.
HIV gets its start in the body by infecting white blood cells called T cells and hijacking cells’ internal machinery. The virus then forces cells to make more HIV copies until the cells finally burst, releasing virus particles into the bloodstream where they find other T cells to infect and begin the destructive process all over again.
Current antiviral therapies can slow the progression of HIV infection and stave off disease, but the drugs can have toxic side effects. Also, HIV can develop resistance to the drugs.
Rossi and his team have been working on alternative ways of disrupting the HIV life cycle and stopping the virus in its tracks.
In previous research, they designed molecules called small interfering RNAs, or siRNAs, that target and shut down genes that HIV needs to multiply. The method has shown some success; however, getting siRNAs into T cells where they can do their job is difficult.
Enter the RNA aptamer.
Rossi’s team developed the aptamer to recognize and attach itself to a key protein that sticks up from the outer surface of HIV.
They found that this RNA aptamer interferes with HIV’s ability to reproduce, but they took it one step further and attached an siRNA to it. Now, the RNA aptamer pulls double duty: It not only interferes with HIV growth, but also acts as a carrier to deliver the anti-HIV siRNA molecule to infected cells.
Testing the combination in laboratory mice, the researchers found promising results.
“Adding the siRNA to the aptamer gave a much longer antiviral effect, lasting several weeks beyond the last dose,” Rossi said.
Further, the new therapy showed no toxic effects.
“The combined aptamer-siRNA agent provides an attractive, nontoxic therapeutic approach for treatment of HIV infection,” Rossi said.
The team now plans to conduct preclinical tests of the new therapy aimed at clearing the way to future human clinical trials, he said, “perhaps in patients who have developed drug-resistant virus.”
City of Hope coauthors on the study included Jiehua Zhou, Ph.D, Haitang Li, Ph.D., David D. Smith, Ph.D., and Piotr Swiderski, Ph.D.