siRNA Technology Stops RSV Infection

Researchers have used small interfering RNA (siRNA) technology to inhibit the NS1 gene of respiratory syncytial virus (RSV), which increases interferon (IFN) production and prevents the virus from avoiding the host immune response and establishing an infection.

Investigators at the University of South Florida (Tampa, USA) prepared plasmids containing siRNA fragments specifically directed against the RSV NS1 gene. When tested in tissue culture, the plasmids reduced RSV replication in A549 cells, but not in IFN-deficient Vero cells. Furthermore, the siRNA induced upregulated expression of IFN-beta and IFN-inducible genes in the A549 cells.

Plasmids were then encapsulated within chitosan nanoparticles, which allowed delivery to the mucous-producing cells that line the lungs. The investigators treated mice intranasally with siNS1 nanoparticles before or after infection with RSV. Results published in the January 2005 issue of Nature Medicine showed a substantial decrease in virus titers in the lung and decreased inflammation and airway reactivity compared to controls.

"This is an exciting advance in the fight against respiratory syncytial virus infection,” said senior author Dr. Shyam S. Mohapatra, Ph.D., director of basic research in the division of allergy and immunology at the University of South Florida. "We found that RNA interference targeting a virus's NS1 gene can be administered in the form of a nasal drop or spray. The treatment keeps the host's natural antiviral shield intact and attenuates virus reproduction, providing substantial protection from severe infections over days to weeks.”





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