Abstract |
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.
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Authors | Bao-jian Li, Qingquan Tang, Du Cheng, Chuan Qin, Frank Y Xie, Qiang Wei, Jun Xu, Yijia Liu, Bo-jian Zheng, Martin C Woodle, Nanshan Zhong, Patrick Y Lu |
Journal | Nature medicine
(Nat Med)
Vol. 11
Issue 9
Pg. 944-51
(Sep 2005)
ISSN: 1078-8956 [Print] United States |
PMID | 16116432
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- RNA, Small Interfering
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Topics |
- Animals
- Antiviral Agents
(therapeutic use)
- Dose-Response Relationship, Drug
- Female
- Genome, Viral
- Lung
(drug effects, pathology, virology)
- Macaca mulatta
- Male
- Mice
- Molecular Sequence Data
- RNA, Small Interfering
(therapeutic use)
- Severe acute respiratory syndrome-related coronavirus
(drug effects)
- Severe Acute Respiratory Syndrome
(drug therapy, pathology, prevention & control)
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