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RNA interference to treat FIP (Winn/Miller Trust grant report)

MT11-007: Effectiveness of Small Interfering RNA (siRNA) to Inhibit Feline Coronavirus Replication, $23,600; Rebecca Wilkes, The University of Tennessee College of Veterinary Medicine

Feline infectious peritonitis (FIP) is a fatal disease in cats. The disease results from widespread viral replication in affected animals and an inadequate and harmful immune response to the virus. Currently, there is no effective treatment for this disease. Though therapies aimed at improving the immune response to this virus have shown some benefit, there is a need for an additional therapy to specifically inhibit virus growth in order to effect a successful treatment. Recently, ribonucleic acid (RNA) interference has been shown to be useful for treating virus infections. This antiviral mechanism results from the introduction of double stranded RNA into cells that specifically target the virus and thus lead to its destruction. This strategy has been used successfully in experimental models to treat Severe Acute Respiratory Disease (SARS), a virus that produces a disease similar to FIP in humans. In addition, this strategy has been shown to be effective against a feline virus, feline herpes virus.

This investigation examined the usefulness of small pieces of RNA (small interfering RNA, siRNA) to inhibit feline coronavirus replication. It is hoped that in combination with immunomodulation, this could prove to be an effective treatment for FIP. The small pieces of RNA actually target the viral genetic material for destruction, leading to decreased virus replication in infected cells. The investigators found that certain combinations of RNA particles offered the best inhibition of virus replication, with reductions of greater than 90% of virus growth in cell culture. The results showed that the siRNA combinations markedly inhibited coronavirus genomic RNA, coronavirus protein, and coronavirus replication in vitro, suggesting a potential therapeutic application of RNA interference in treating FIP. [MK]