Monday, February 26, 2007

Carbon Nanotubes versus HIV

Nanotubes can transport RNA into the human immune system's white blood cells, making the cells less vulnerable to attack by the HIV virus.

By Prachi Patel-Predd

Nanotube carriers: Receptor proteins on human T cells are dyed red (top image). The HIV virus binds to these receptors and attacks T cells, but pieces of RNA can be used to turn off the receptors’ expression. Stanford University researchers have shown that carbon nanotubes could be used to transport RNA into the T cells, turning off the receptors’ expression (bottom). Credit: Zhuang Liu, Stanford University

Researchers at Stanford University have added one more trick to carbon nanotubes' repertoire of accomplishments: a way to fight the human immunodeficiency virus (HIV). Chemistry professor Hongjie Dai and his colleagues have used carbon nanotubes to transport RNA into human white blood cells that defend the body from disease, making the cells less susceptible to HIV attack.

The recently discovered technique of RNA interference (RNAi)--using snippets of RNA to shut down disease-causing genes--could be an important weapon against diseases such as cancer and AIDS. (See "Prescription RNA.") Researchers have shown that one way to combat HIV with RNAi is to switch off a gene that controls the expression of receptor proteins on the surface of white blood cells known as T cells; the virus binds to this receptor and then enters and infects the T cells. If interfering RNA could turn off the receptors, the virus would have no point of entry into the cells. However, RNA can't easily cross cell membranes and enter cells on its own, and researchers are trying to find a way to get the RNA into cells more efficiently.

In a paper now online in the journal Angewandte Chemie, Dai and his colleagues at Stanford's Division of Infectious Diseases describe attaching RNA to carbon nanotubes, which enter T cells and deliver the RNA. When the researchers placed T cells in a solution of the carbon nanotube-RNA complex, receptor proteins on the cell surfaces went down by 80 percent. Carbon nanotubes are known to enter many different types of human cells, although researchers don't understand exactly how they do it. Some experts suspect that because of their long, thin shape, nanotubes enter cells much as a needle passes through skin.

The new work is an important step toward using carbon nanotubes for RNAi therapy, says Bruce Weisman, a chemistry professor at Rice University, even though "it's still a long way from any kind of medical applications."

"This is a very interesting new approach," says Judy Lieberman, a senior investigator at the Harvard Medical School Center for Blood Research. "But it's a little early to know if it's going to work in vivo [inside the body]." Lieberman says that the potential toxicity of the nanotubes would be the biggest concern for a therapeutic application. She believes that the researchers will need to do more-extensive toxicity studies before they can establish that the nanotubes are completely safe for use in humans.

So far, the Stanford researchers kept T cells in the nanotube solution for three days, and they found that the cells didn't die faster or abnormally. "We have also performed a thorough in vivo toxicity study of our nanotubes with mice and observed no obvious side effect," Dai says.

The Stanford researchers are now working on an important next step: a cell-targeting mechanism for the nanotubes. If they are used for RNA therapy, the nanotubes will have to be tailored to target only T cells when they are injected into the patient's bloodstream. "Potentially, we can conjugate certain peptides or antibodies with the nanotubes to enable targeting of certain types of cells, including T cells," Dai says.

Even then, the technique will face other challenges inside the body, Lieberman says. Scavenger cells that are designed to filter blood could take the nanotubes up, for instance, or the nanotubes might not transport RNA into T cells that are in tissue and not in the blood circulation. "Some HIV-infected cells are in lymph nodes or the gut, so I don't know if these nanotubes would get there," Lieberman says.