[Edit: Hadn't noticed, this seems to have been published in Hepatology and was posted by Nigel 6/7.]
First Demonstration of Systemic siRNA Efficacy at Therapeutically Relevant Doses is Published by Sirna Therapeutics
Monday July 25, 7:22 am ET
Breakthrough research published in Nature Biotechnology describes significant anti-viral activity of chemically optimized siRNA
SAN FRANCISCO and BOULDER, Colo., July 25 /PRNewswire-FirstCall/ -- Sirna Therapeutics, Inc. (Nasdaq: RNAI - News) announced today the publication in Nature Biotechnology of a breakthrough study demonstrating a 95% knockdown of hepatitis B virus (HBV). In the study, Sirna used its chemically optimized short interfering RNA (siRNA) at 1, 3 and 5 mg/kg together with encapsulation and delivery technology provided by Protiva Biotherapeutics Inc. This is the first demonstration of systemic siRNA efficacy at therapeutically relevant doses and establishes a strong scientific foundation for broad human application of RNAi-based therapeutics.
The study demonstrated that Sirna's chemically optimized and encapsulated siRNAs have high potency and prolonged duration of activity in vivo. The siRNA formulation, targeting HBV, was administered by standard intravenous injection to mice carrying replicating HBV. Three therapeutically relevant doses of 1, 3, or 5 mg/kg resulted in up to a 95% dose dependent reduction in serum HBV DNA levels. A similar reduction was observed in Hepatitis B Surface Antigen protein levels. The anti-viral activity persisted for at least seven days.
This unprecedented efficacy correlates with a significantly longer circulation time of siRNAs in blood plasma and residence time in the liver compared to unmodified and non-encapsulated siRNAs. Importantly, Sirna modified and optimized the siRNAs used in the study to abrogate the induction of serum interferon-alpha (IFN-alpha) and inflammatory cytokines (IL-6, TNF-alpha) thereby further demonstrating Sirna's capability to chemically modify RNAi-based therapeutics to modulate cellular responses.
"We are extremely pleased by the significant knockdown of HBV with low doses of our encapsulated siRNA," stated Sirna Senior Vice President and Chief Scientific Officer, Barry Polisky, PhD. "With these results, we have established a new benchmark for siRNA efficacy in vivo. This is the second study published by Sirna scientists that validates the efficacy of chemically optimized siRNAs in vivo. These robust results further underscore Sirna's leadership position and extensive experience in RNA biology and chemistry. Sirna is building on these landmark results as we focus our human clinical program on hepatitis C. We continue to improve the efficacy of our anti-viral compounds through proprietary modification and delivery approaches and plan to initiate hepatitis C clinical trials next year."
Ian MacLachlan, PhD, Chief Scientific Officer of Protiva Biotherapeutics Inc., said, "The high degree of efficacy observed in this study is superior to all other previously reported data for any systemically delivered siRNA and is a direct result of combining Sirna's expertise in chemical modifications with Protiva's encapsulation and delivery technology."
Sirna initiated primate studies in its hepatitis C program in June 2005 and expects to commence Phase I human clinical trials in 2006. |
