Emerging infectious diseases pose the threat of a looming global pandemic. As illustrated by the outbreak of the SARS coronavirus (SCV) in 2003, there is a pressing need for new effective treatments that can be rapidly developed in response to previously unknown viruses. Reporting in *Nature Medicine*, Li *et al*. took a step towards this goal by demonstrating that intranasal delivery of SARS-specific small interfering RNA (siRNA) was effective against SARS in a rhesus macaque model --- providing hope that siRNA could provide the means to move rapidly from gene sequence to targeted therapeutics for many previously intractable diseases.

The recently established rhesus macaque SARS model, based on intranasal instillation of a highly virulent SARS strain, mirrors the sequence of pathologies in humans with SARS. Taking advantage of previously identified siRNA sequences that have a synergistic anti-SCV effect *in vitro*, the authors used a clinically approved aqueous carrier solution (D5W) to intranasally administer the therapeutic siRNA either 4 hours before, concurrently or 4 hours after infection of the animals with SCV. The effectiveness of this treatment was evident as macaques from all three treatment regimes had a lower increase in body temperature, reduced viral loads and a reduced level of lung damage, indicating potent suppression of SCV-induced SARS pathology compared with SCV-infected animals that received no siRNA or unrelated siRNAs.

These results might be attributable to a protective effect conferred by siRNA on cells against SCV infection (the prophylactic treatment could even lead to direct degradation of viral RNA by pre-existing siRNA in the upper airway tract upon entry of the viral particle); the inhibition of viral protein synthesis in infected cells caused by the degradation of SCV mRNA; or preventing the replication of the SCV genome and the spread of virions to uninfected cells. As neutralizing antibodies were also detected soon after infection, the authors speculated that several antiviral mechanisms were operative.

Importantly, the effect of the siRNA did not seem to be caused by the induction of a pro-inflammatory interferon response, which can potentially exacerbate symptoms and lung damage. Specific emphasis was placed on tolerability and safety --- as siRNA-treated animals showed no evidence of inflammation or toxicity not attributable to the SCV infection, intranasal administration of siRNA could hold tremendous potential for new prophylactic and therapeutic treatment strategies.

This first successful therapeutic use of siRNA in primates provides further support for the growing expectation that siRNA will provide a powerful new means to combat emerging infectious diseases, which could translate into massive reductions in development time for new targeted therapeutics.
