RNA Interference Blocks Hepatitis C Virus Replication

By Jason Socrates Bardi

In the less complicated times of the Gilded Age 100 years ago, aspiring debutantes had simply to have themselves announced as they entered a room to make a splash in society. Today, they have to hope for an appearance in the Sunday Styles section of the New York Times to announce that they have arrived.

On Tuesdays, technologies, like debutantes, face the eyes of the public on the pages of the New York Times. Whatever technology, molecule, or theory appears in the Science Times section has truly arrived.

Last month, RNA interference was featured in a Science Times article describing how a team of scientists had used the technique to selectively knock out genes of a worm.

Now a recent study by Professor Frank Chisari and Research Associates Sharookh Kapadia and Amy Brideau-Andersen in the Department of Molecular and Experimental Medicine has applied the technique of RNA interference to knock out genes in a different organism—the hepatitis C virus (HCV). HCV is a major cause of chronic liver disease in the United States and currently infects some 3.9 million Americans, estimates the Centers for Disease Control (CDC), and over 180 million people worldwide.

A couple of years ago, Chisari heard a lecture by Phillip Sharp, a Nobel laureate and a professor of biology at the Massachusetts Institute of Technology, describing RNA interference (RNAi), a natural antiviral mechanism of plants that had also been used to inhibit gene expression in worms and fruit flies. In his lecture, Sharp described the use of RNA interference to shut down cellular gene expression in mammalian cells.

Chisari immediately recognized that RNAi should also be able to shut off viral gene expression in human cells, and last week, in an article published online by the Proceedings of the National Academy of Sciences, Chisari, Brideau-Andersen and Kapadia report that RNA interference can inhibit HCV replication in tissue culture. Others have shown that RNAi can inhibit HIV, poliovirus and rotavirus replication as well.

The technique involves delivering small, 20- to 30-base pieces of double stranded RNA into a cell. Once inside the cell, these short sequences anneal to complementary regions of cellular or viral RNA and trigger an intracellular response that specifically destroys the target RNA. If the RNA is viral in origin, this response can silence the target gene and prevent viral replication.

Though the technique is in its infancy, and many technical barriers must be overcome before any drug based on RNA interference reaches the pharmacist's shelf, it does hold great promise for the treatment of HCV and other infections, says Chisari. The technique is of immediate interest in basic science because it can be used to selectively shut off normal cellular genes in a developing or a mature organism, permitting scientists to study the impact of the absence of the corresponding gene products on cellular function and tissue development.

To read the article, "Interference of hepatitis C virus RNA replication by short interfering RNAs" by Sharookh B. Kapadia, Amy Brideau-Andersen, and Francis V. Chisari, please see:






The top panel shows parental cells stained in blue. The middle panel shows cells infected with hepatitis C virus (HCV) cells and the baseline level of HCV replication, in red. The bottom panel shows the greatly reduced level of HCV replication four days after the cells were transfected with the HCV-specific short interfering RNAs, shown in green. Click to enlarge.