A new genetic tool may be the answer to disrupting HIV’s life cycle and stopping the virus in its tracks.
A new method of targeting the virus that causes AIDS may provide a powerful one-two punch against the disease. The strategy could improve HIV-positive patients’ chances of overcoming the infection.
Scientists led by John J. Rossi, Ph.D., Lidow Family Research Chair in the Department of Molecular and Cellular Biology, developed a small piece of genetic material — called an RNA aptamer — that both interferes with HIV’s ability to infect cells and carries with it another anti-HIV molecule. They reported their advance in Science Translational Medicine.
HIV gets its start in the body by infecting certain white blood cells and hijacking the cells’ internal machinery. The virus then forces the cells to make more HIV copies until the cells burst, releasing virus particles into the bloodstream. There, they infect more cells and begin the destructive process all over again.
Current antiviral therapies can keep HIV infection from progressing and stave off disease, but the drugs can have toxic side effects. Also, HIV can grow resistant to them. 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, which target and shut down genes that HIV needs to multiply. However, getting siRNAs into the white blood 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 a siRNA to it. Now, the RNA aptamer 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 — and it showed no toxic effects.
The team now plans to conduct preclinical tests of the new therapy aimed at clearing the way to future human clinical trials, perhaps in patients who have developed a drugresistant virus, Rossi said.