Nature Medicine
11, 944 - 951 (2005)
Published online: 21 August 2005; | doi:10.1038/nm1280
Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaqueBao-jian Li1, 2, 7, Qingquan Tang3, 7, Du Cheng2, 7, Chuan Qin4, 7, Frank Y Xie2, 3, Qiang Wei4, Jun Xu3, Yijia Liu3, Bo-jian Zheng5, Martin C Woodle3, Nanshan Zhong6
& Patrick Y Lu31
Biotechnology Research Center of Sun Yatsen University, and Key Laboratory of Gene Engineering of Ministry of Education of the State, Guangzhou, China. 2
Guangzhou Top Genomics, Ltd., Guangzhou, China. 3
Intradigm Corporation, 12115 K Parklawn Drive, Rockville, Maryland 20852, USA. 4
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 5
Department of Pathology, University of Hong Kong, Hong Kong, China. 6
Guangzhou Institute of Respiratory Diseases, Guangzhou, China. 7
These authors contributed equally to this work.
Correspondence should be addressed to Patrick Y Lu patricklu@intradigm.com or Nanshan Zhong nanshan@vip.163.com 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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