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RNAi therapeutic successful for treatment of SARS respiratory virus in Rhesus Macaque

Published on September 12, 2005 at 8:44 AM · No Comments

Intradigm Corporation announced today its collaboration with Chinese academic and biotech groups has achieved clear evidence of prophylactic and therapeutic effects of siRNA (small interfering RNA) agents in Rhesus monkey to treat SARS coronavirus (SCV) respiratory infection.

The results are published as a research article in the September 2005 issue of Nature Medicine.

The published results show that potent siRNA inhibitors against SCV, validated in previous in vitro study (Antiviral Therapy 9:365-374), are active in vivo using a mouse model system and subsequently in a rhesus macaque (Macaca mulatta) SARS disease model, using a clinically viable delivery formulation by intranasal administration. The studies in macaques included two control groups and three treatment groups, using prophylactic, concurrent or early post exposure regimens, with a large number of animals in each group for statistically meaningful results. A pair of siRNA oligos, SC2 and SC5, targeting two different genes in the virus genome were administrated at 10 to 40 mg/kg. The numerous observations, including clinical SARS-like symptoms, lung histopathology and levels of viral RNA, confirm achievement of an siRNA- mediated inhibition of the respiratory virus and, importantly, no sign of siRNA treatment-mediated toxicity or off target effects. These results provide strong support for clinical investigation. Most importantly the results clearly illustrate the prospects for siRNA therapeutics to address unmet clinical need but also to dramatically reduce the time and cost of drug development. This capability is especially important in the critical area of newly emerging respiratory viral infections.

Nature Medicine also recognized the importance of the work in a news release entitled "New treatment against SARS effective in monkeys," which claimed that, "These results constitute the first successful therapeutic use of siRNA in primates, and significantly boost up the potential of this tool to prevent and treat SARS in people."

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