๐ Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque
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.
keywords
๐ severe acute (1373)
๐ infectious disease (312)
๐ respiratory syndrome (2004)
๐ results suggest (206)
๐ acute respiratory (1734)
๐ infectious diseases (94)
author
๐ค Li, Bao Jian
๐ค Tang, Qingquan
๐ค Cheng, Du
๐ค Qin, Chuan
๐ค Xie, Frank Y.
๐ค Wei, Qiang
๐ค Xu, Jun
๐ค Liu, Yijia
๐ค Zheng, Bo Jian
๐ค Woodle, Martin C.
๐ค Zhong, Nanshan
๐ค Lu, Patrick Y.
year
โฐ 2005
journal
๐ Nature Medicine
issn
๐ 10788956
volume
11
number
9
page
944-951
citedbycount
305
download
๐ [BibTeX]