title: Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque.
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.
authors.affiliation: Biotechnology Research Center of Sun Yatsen University, and Key Laboratory of Gene Engineering of Ministry of Education of the State, Guangzhou, China.
authors.forename: Bao-jian
authors.initials: BJ
authors.lastname: Li
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Tang
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Xie
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Yijia
authors.initials: Y
authors.lastname: Liu
authors.forename: Bo-jian
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Martin C
authors.initials: MC
authors.lastname: Woodle
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Lu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016679:Genome, Viral; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000998:Antiviral Agents; D034741:RNA, Small Interfering