Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in rhesus macaque

Development of therapeutic agents for severe acute respiratory syndrome ( SARS) viral infection using short interfering RNA ( siRNA) inhibitors exemplifies a powerful new means to combat emerging infectious diseases. Potent siRNA inhibitors of SARS coronavirus ( SCV) in vitro were further evaluated for efficacy and safety in a rhesus macaque ( Macaca mulatta) SARS model using clinically viable delivery while comparing three dosing regimens. Observations of SARS- like symptoms, measurements of SCV RNA presence and lung histopathology and immunohistochemistry consistently showed siRNA- mediated anti- SARS efficacy by either prophylactic or therapeutic regimens. The siRNAs used provided relief from SCV infection - induced fever, diminished SCV viral levels and reduced acute diffuse alveoli damage. The 10 - 40 mg/ kg accumulated dosages of siRNA did not show any sign of siRNA- induced toxicity. These results suggest that a clinical investigation is warranted and illustrate the prospects for siRNA to enable a massive reduction in development time for new targeted therapeutic agents.