RNAi solution knocks down herpes infection

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Ever since RNA interference hit the scene a few years ago as a way to selectively turn off gene expression, researchers have been investigating whether these small but powerful bits of RNA can be used as therapies. The problem has been delivery – how to get the RNA into the cell where it can silence gene expression. A study in the Nov. 23, 2005 Nature showcases a novel therapeutic approach for RNAi – as a vaginal microbicide that can reduce genital herpes virus infection in mice. The result of a collaboration between the labs of Judy Lieberman and David Knipe, the study shows that small interfering RNAs (siRNAs) can be readily taken up by mucosal surfaces of the body and reduce viral infection.

Lieberman, Harvard Medical School professor of pediatrics at the CBR Institute for Biomedical Research, has been working with RNAi as a potential therapy for HIV infection. She suspected that siRNAs might be delivered more easily to the vaginal surface than to other tissues as part of a microbicide for HIV. Deborah Palliser, HMS instructor in pediatrics at Children’s Hospital Boston and CBR, began working with Lieberman to investigate the usefulness of an siRNA-based microbicide. First they tested the concept using a mouse that expresses green fluorescent protein (GFP) in each of its cells. When Palliser treated the mice intravaginally with GFP siRNA, the treatment turned off GFP at the surface of the genital tissue and even into the supportive stromal layer beneath the vaginal lining. “What we found very surprising is the degree or the depth to which it was taken up,” Palliser said.

Though their ultimate goal is to target HIV, Palliser and Lieberman decided to test the approach on herpes virus-2 (HSV -2) infection, which can be studied more easily in mice. They teamed up with Knipe, the Higgins professor of microbiology and molecular genetics at HMS, and Qing-Yin Wang, a postdoctoral fellow in his lab, who had already developed a mouse model of herpes infection. Knipe identified viral genes that are necessary for the virus to replicate in cells and that would make good targets for siRNA silencing.