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

Nat Med. 2005 Sep;11(9):944-51. doi: 10.1038/nm1280. Epub 2005 Aug 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Genome, Viral
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Macaca mulatta
  • Male
  • Mice
  • Molecular Sequence Data
  • RNA, Small Interfering / therapeutic use*
  • Severe Acute Respiratory Syndrome / drug therapy*
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Severe acute respiratory syndrome-related coronavirus / drug effects*


  • Antiviral Agents
  • RNA, Small Interfering

Associated data

  • GENBANK/AY274119
  • GENBANK/AY350750
  • RefSeq/NC_004718