Study Finds RNAs Play Important Role as Antiviral Agents for Cell Treatments

City of Hope
Monday, 1 March 2004

Findings Could Lead to New Ways of Treating HIV/AIDS, Other Viruses

A new study describes for the first time that certain genetic molecules can trigger a strong, natural antiviral mechanism in the body's cells. The discovery could lead to new methods of treating patients with HIV/AIDS, hepatitis and other viruses.

The molecules, called small interfering RNAs (siRNAs), are shown to be potent inducers of interferon when they contain a certain modification on their ends. Interferons are proteins that inhibit viral growth in cells, according to the City of Hope Cancer Center research published in today's edition of the journal Nature Biotechnology.

RNA, or ribonucleic acid, which controls chemical activities in cells, is closely related to DNA and has traditionally been associated with the expression of genes. However, research developments in recent years have shown the molecule to have a much broader role in the cell than was previously understood. In fact, siRNAs were named 2001's "Molecule of the Year" by the journal Science for their potential to revolutionize biomedical research and treatment. Since then, these molecules have been getting more attention.

The latest development "demonstrates that siRNAs that have a specific chemical group, called tri-phosphate, on one end of the molecule can cause a cell to produce interferon," said the study's principal investigator, John Rossi, Ph.D., Chair, Division of Molecular Biology, City of Hope.

This ability in the cell may even be useful in the treatment of cancers, if the interferon trigger results in the killing of diseased cells. Dr. Rossi said the research also may provide a link to observations that certain "engineered" short RNAs trigger interferon responses, since these RNAs have tri-phosphates, the specific chemical group, at their 5-prime, or front ends. He said it is highly likely that the cellular response reflects an innate immune response to viral infections that generate tri-phosphate containing RNAs within cells.

This research is the latest in a large body of RNA studies by Dr. Rossi and his colleagues. Last year, he co-authored a study in which researchers placed genetically engineered anti-HIV siRNAs into human blood-forming stem cells. The stem cells then produced T-cells and macrophanges, the primary targets of HIV infection, which maintained their resistance to HIV.

The research team at City of Hope's Beckman Research Institute included Dong-Ho Kim, Ph.D., Beckman Research Fellow; Michael Longo, B.S, research associate; and Young Han, B.A., research associate, all of the Division of Molecular Biology; and Patric Lundberg, Ph.D., assistant research scientist, Division of Virology; and Edouard Cantin, Ph.D., associate chair and professor, Division of Virology.

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