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HIV-1 virus replication inhibited in lab by RNA interference

January 06, 2010

A form of RNA developed at MIT has inhibited replication of HIV-1 virus in human-derived cell lines, potentially showing a new way to combat AIDS. The in-vitro work uses RNA interference (RNAi), a naturally occurring technology used by a variety of organisms to silence genes.

"If many obstacles can be surmounted, this could be a basis for intervention in HIV treatment," said Professor Phillip A. Sharp, director of MIT's McGovern Institute for Brain Research, who shared the Nobel Prize in 1993 for his discovery of the "nonsense" segments of the DNA molecule and RNA splicing.

Those obstacles include finding methods to deliver the short interfering RNAs to cells in animals or humans, and ensuring that the process won't have negative side effects. The study, published this week online in Nature Medicine, involved four laboratory heads at MIT, Harvard Medical School and the University of Pennsylvania School of Medicine.

The researchers created short interfering RNAs (siRNAs) and demonstrated how these siRNAs can inhibit the growth of HIV through gene silencing. They showed specific examples of regions of the HIV genome and regions of cellular genes that can be targeted to inhibit viral infections.

Carl Novina from the Center for Cancer Research, the lead author of the study, used the analogy of a radio to explain how the RNA interference works to silence genes. "The central tenet of biology is that DNA makes RNA and RNA makes protein. RNA interference acts like a switch, like the volume control on a radio, to turn down the volume of gene expression," he said.

The other lead researcher was Premlata Shankar of the Center for Blood Research and the Department of Pediatrics at Harvard Medical School.

The researchers found two ways of using siRNA technology to potentially inhibit HIV infection. The first is by silencing cellular genes that are essential to HIV infection, thereby making the cells less susceptible to the HIV virus.

The second type of intervention is to use siRNAs to silence the HIV gene itself. Five days after introducing the siRNAs into the cells, virus production was reduced 25-fold, compared to controls.

The work will assist other researchers as they continue to use the siRNA technology in the search for a therapeutic setting, where a drug or gene therapy approach can potentially be used to inhibit HIV and other viral replication.


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