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.

On the double: A highly packed interlayer‐crosslinked micelle (HP‐ICM) with pH and reduction sensitivity was developed for targeted drug release (see picture; DTT=dithiothreitol, red circles=doxorubicin). The HP‐ICM suppresses drug leakage in blood circulation while rapidly releasing drug inside lysosomes of cancer cells. Biological studies revealed the potential of the dual‐sensitive HP‐ICM in cancer treatment.

A novel multifunctional polymeric micelle bearing a pH‐tunable on‐off module for programmed drug release, folate for tumor targeting, and quantum dots for fluorescent imaging is described. The micelle can turn drug release off at neutral pH whereas on inside lysosomes. QD functionalization allows a clear elucidation of pH‐tunable drug release and facile visualization of in vivo delivery event.

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A novel reduction and pH dual-sensitive nonviral vector for long-circulating and tumor-targeted siRNA delivery is described. The nanomedicine is negatively charged at neutral pH of bloodstream whereas it is positively charged at lower pH of tumor tissue (ca. 6.8). Interlayer crosslinking with disulfide bonds stabilizes the nanomedicine during blood circulation and allows quick intracellular siRNA release after endocytosis.