Potent New Weapon In Fight Against HIV: Cell Manipulation Can Block And Destroy The Virus

City of Hope
Tuesday, 30 April 2002

Scientists have demonstrated a new and powerful method for killing HIV, the virus that causes AIDS, by enlisting an infected cell's own machinery to dice up viral genetic messages. The research could fundamentally change the course of AIDS gene therapy investigations.

"This could be the smart bomb in our arsenal," said John Rossi, Ph.D., who chairs the Division of Molecular Biology at City of Hope Cancer Center and Beckman Research Institute. The findings of Rossi's research team appear in the May issue of Nature Biotechnology.

Rossi and his co-investigators enlisted a novel mechanism in cells in which small pieces of RNA, called small interfering RNA or "siRNA," are involved with inhibiting viral growth in infected cells. Using this naturally occurring machinery, Rossi's team engineered human cells to make the siRNA that directs the machinery to dice up the genetic material necessary for HIV to grow.

"We've, in effect, given the army on standby the key weapon it needs to find and destroy the invading enemy," said Rossi.

This study builds on City of Hope's expertise in HIV research, which in the past has resulted in a groundbreaking clinical trial using ribozymes, or "molecular scissors," to combat the virus. The current method uses technology developed from the previous research, and patented by City of Hope, to supply infected cells with the siRNA necessary to recognize and destroy viral genetic messages.

In fact, Dr. Rossi's team is combining the siRNA approach with ribozymes that destroy the message for a cellular co-receptor used by the virus along with specialized RNA decoys that sequester HIV proteins from the virus. The goal of the combined approach is to maximize cellular protection from viral infection and minimize the probability of viral escape mutants.

The research team included Nan Sook Lee, Ph.D.; Taikoh Dohjima, M.D.; Gerhard Bauer, M.S.; Haitang Li, M.S.; Ming-Jie Li, Ph.D.; Ali Ehsani, Ph.D; and Paul Salvaterra, Ph.D., all of City of Hope National Medical Center and Beckman Research Institute.

The cellular devices could be introduced to patients as early as next year, Rossi said. Future research will involve introducing the mechanism into other kinds of cells.

For more information, or to contact City of Hope, see their website at: www.cityofhope.org